|Year : 2021 | Volume
| Issue : 4 | Page : 336-341
Efficacy of intrathecal fentanyl versus buprenorphine as an adjuvant to isobaric levobupivacaine in lower limb surgeries: a comparative study
Preet Hiten Furia, Vasanti Mukund Sasturkar, Sanhita J Kulkarni, Pradnya Shripad Joshi, Pramod V Bhale
Department of Anesthesia, MGM Medical College and Hospital, Aurangabad, Maharashtra, India
|Date of Submission||01-Jul-2021|
|Date of Acceptance||17-Nov-2021|
|Date of Web Publication||22-Dec-2021|
Dr. Vasanti Mukund Sasturkar
Department of Anesthesia, MGM Medical College and Hospital, MGM Campus, N-6, Cidco, Aurangabad 431003, Maharashtra.
Source of Support: None, Conflict of Interest: None
Background: Fentanyl and buprenorphine are the most commonly used adjuvants in spinal anesthesia. There is paucity in literature regarding the comparison of these two adjuvants when used with levobupivacaine. Aim: This study aimed to compare the efficacy and safety of fentanyl and buprenorphine added to isobaric levobupivacaine. Materials and Methods: This prospective randomized double-blind study was undertaken on 60 patients between the ages of 18 and 65 years with the American Society of Anesthesiologists (ASA) physical status 1, 2, and 3 scheduled for lower limb surgery. Group LF (n = 30) received 3-mL isobaric 0.5% levobupivacaine with 10 microgram (mcg) injection fentanyl and Group LB (n = 30) received 3-mL isobaric 0.5% levobupivacaine with 60 mcg injection buprenorphine. Characteristics of sensory and motor blockade, duration of postoperative analgesia, hemodynamic parameters, and adverse effects were recorded. Data were analyzed by appropriate statistical tests and a value of P < 0.05 was considered significant. Results: The onset of sensory block and duration of motor block in both groups were comparable (P > 0.05). The onset of motor block, duration of sensory block, and duration of analgesia were significantly prolonged in Group LB than Group LF (P < 0.05). Six patients in Group LF and three patients in Group LB developed nausea, although the difference was not statistically significant (P = 0.2801). None of the patients in either of the study groups had adverse effects such as bradycardia, hypotension, pruritus, or respiratory depression. Conclusion: Combinations of 0.5% isobaric levobupivacaine (3 mL) with fentanyl (10 mcg) and buprenorphine (60 mcg) show a good safety profile when administered intrathecally, although combination of levobupivacaine–buprenorphine is superior in terms of prolonged sensory block and longer duration of postoperative analgesia.
Keywords: Buprenorphine, fentanyl, intrathecal, isobaric, levobupivacaine
|How to cite this article:|
Furia PH, Sasturkar VM, Kulkarni SJ, Joshi PS, Bhale PV. Efficacy of intrathecal fentanyl versus buprenorphine as an adjuvant to isobaric levobupivacaine in lower limb surgeries: a comparative study. MGM J Med Sci 2021;8:336-41
|How to cite this URL:|
Furia PH, Sasturkar VM, Kulkarni SJ, Joshi PS, Bhale PV. Efficacy of intrathecal fentanyl versus buprenorphine as an adjuvant to isobaric levobupivacaine in lower limb surgeries: a comparative study. MGM J Med Sci [serial online] 2021 [cited 2022 Jan 18];8:336-41. Available from: http://www.mgmjms.com/text.asp?2021/8/4/336/333316
The Original Article has been transcribed out of a dessertation of Preet Hiten Furia, one of the authors, submitted by him to MGM Medical College and Hospital, Aurangabad, Maharashtra, India for the award of MD (Anesthesiology) Degree. It is certified that neither the dessertation has been published in any format anywhere nor it will be published in the future. Permission has been obtained from the management of the college for the publication of the manuscript in the proposed journal.
| Introduction|| |
Bupivacaine has been the gold standard drug for spinal anesthesia. Levobupivacaine, S(–)enantiomer of racemic bupivacaine, has similar sensory and motor block characteristics but a lower incidence of cardiovascular toxicity than intrathecal bupivacaine when studied in humans and animals,, and can be used as an alternative to bupivacaine for spinal anesthesia.
Intrathecal adjuvants such as opioids, clonidine, ketamine, and dexmedetomidine are used in combination with local anesthetic agents to prolong the effect of spinal anesthesia. Opioids such as fentanyl and buprenorphine are most common among them. There are very few studies regarding the intrathecal use of levobupivacaine and fentanyl in lower limb surgeries and even fewer studies of intrathecal levobupivacaine and buprenorphine. We did not come across any published literature where the efficacy of the two aforementioned intrathecal drug combinations was compared; hence, we decided to compare the efficacy and safety of intrathecal 0.5% isobaric levobupivacaine–fentanyl and levobupivacaine–buprenorphine in lower limb surgeries. We hypothesized that levobupivacaine–buprenorphine would be a better drug combination than levobupivacaine–fentanyl.
The primary objective of our study was to compare sensory and motor block characteristics and the duration of postoperative analgesia. The secondary objectives were to compare intraoperative hemodynamic stability and adverse effects, if any, associated with the administration of study drugs.
| Materials and methods|| |
This prospective randomized double-blind study was conducted after obtaining written permission from the Institutional Ethics Committee for Research on Human Subjects, MGM Medical College, Aurangabad, Maharashtra, India vide their letter no. MGM-ECRHS/2018/30 dated October 5, 2018.
For calculating sample size, we conducted a pilot study with 10 patients in each group. On the basis of the results of this pilot study and setting the α error at 0.05 and β error at 0.9, the sample size was calculated as follows:
where M1 is the mean test intervention (=3.60), M2 is the mean control intervention (=2.65), Z1 is the Z value associated with α (=1.64), Z2 is the Z value associated with β (=1.28), S1 is the standard deviation (SD) of M1 (=1.34), S2 is the SD of M2 (=0.95), S is the pooled SD (=1.161), and n is number of patients in each group (=25).
A power analysis indicated that 25 patients per group were required to detect a 10% difference in duration of analgesia. Considering the dropouts, we recruited 30 patients in each group.
All the patients were screened before enrolment in the study. Patients of both sexes between the ages of 18 and 65 years with the American Society of Anesthesiologists (ASA) physical status 1, 2, and 3 scheduled for lower limb surgery were enrolled for the study. Pregnant mothers, lactating mothers, patients with severe hepatic and renal dysfunction, severe left ventricular systolic dysfunction (EF <30%), preexisting severe bradycardia, and patients with known allergy to the study drugs were excluded from the study. A voluntary written informed consent was taken from all the eligible and willing patients. Before enrolment of the first patient, the study was registered in the clinical trial registry of India (registration no. CTRI/2019/01/017093).
Sixty patients were randomly divided using the sealed envelope method into two groups of 30 patients each. Group LF received 3-mL isobaric 0.5% levobupivacaine with 10 microgram (mcg) injection fentanyl (total 3.2 mL) and Group LB received 3-mL isobaric 0.5% levobupivacaine with 60 mcg injection buprenorphine (total 3.2 mL). One anesthesiologist who was not part of the study administered the allocated drug intrathecally, whereas another anesthesiologist (investigator) recorded the findings. Both the patient and investigator were blind to the study drug used making the study double-blind.
On the day of surgery in the operation theatre, monitors were attached and baseline parameters such as heart rate (HR), noninvasive mean blood pressure (MAP), oxygen saturation (SPO2), and electrocardiogram (ECG) were recorded. Intravenous (IV) access was established using a 20-G IV cannula. Coloading was done by infusion of 500-mL Ringer’s lactate solution. HR and blood pressure (mean) were recorded.
Spinal anesthesia was administered in a sitting position in the L3–L4 intervertebral space using a 23-G Quincke spinal needle under all aseptic precautions. After making the patient supine, the sensory block was tested by pinprick in mid axillary line every 3 min till peak sensory level, that is, two consecutive readings at the same dermatomal level were achieved. Thereafter, the sensory block was tested every 20 min till the block regression to L1 level. The time from the spinal injection (T-0) to the time taken to achieve T10 level was considered as the onset of sensory blockade. The time from T-0 to L1 regression was taken as the total duration of the sensory block.
Motor block was tested every 3 min using a modified Bromage scale from intrathecal injection till starting of surgery. The onset of motor block was taken as the time from T-0 to obtaining a motor block of grade 2. Thereafter, motor block was tested in the postoperative period every 20 min till complete recovery (grade 0) and the duration of the motor block was considered from achieving grade 2 till complete recovery to grade 0. Surgery was allowed after achieving sensory block up to T10 and grade 2 motor block. Failure to achieve the required block in 20 min was considered as a failure of block and general anesthesia was administered to those patients.
After spinal anesthesia was administered, HR and MAP were recorded every 3 min for the first 20 min and thereafter every 10 min till regression of sensory block to L1. A decrease in the MAP by more than 20% of baseline was considered as hypotension and treated with injection mephentermine 5 mg IV. Decrease in the HR less than 50 beats/min was taken as bradycardia and treated with injection atropine 0.6 mg IV. Injection ondansetron 4 mg IV was given to treat intraoperative nausea/vomiting.
Postoperatively, the pain was assessed using a visual analog scale (VAS) every 30 min for the first 2 h and then every 2 hourly till the VAS score reached >4 and analgesia in the form of injection tramadol (100 mg) IV was given at that time. Duration of analgesia was considered as time from the spinal injection (T-0) till administration of the first dose of rescue analgesia.
Quantitative data were expressed in form of mean ± SD for statistical analysis; the unpaired t test was used for comparison of mean between two groups. The paired t test was used for intragroup comparison. Qualitative data were expressed in the form of frequency and percentage. The chi-square test was used for qualitative data. Data were analyzed by using the Statistical Package for the Social Sciences (SPSS) software program, version 20.0 for Windows. A value of P < 0.05 was regarded as statistically significant and a value of P < 0.001 as highly significant.
Consort flow diagram
| Results|| |
Demographic data were comparable in both groups. All the patients in both groups had adequate sensory and motor block for the surgery [Table 1].
The mean onset of sensory block among patients in both groups was comparable (P = 0.309). The maximum level of sensory blockade attained in both the groups was T6 (n = 5 in Group LF and n = 2 in Group LB) showing no statistically significant difference (P = 0.083). The median sensory level of the block was T10 in both groups. The mean duration of sensory block was prolonged in Group LB (187.7 ± 19.8 min) than Group LF (161.7 ± 13.7 min). This difference was highly statistically significant (P = 0.000). The mean time taken for the onset of motor blockade was prolonged in Group LB than in Group LF. The difference was statistically significant (P = 0.040). The duration of the motor blockade in both groups was comparable. (P = 1.000). The duration of analgesia was significantly prolonged in Group LB (475.7 ± 45.3 min) than in Group LF (432.7 ± 48.6 min) (P = 0.001) [Table 2] and [Figure 1].
|Figure 1: Comparison of maximum level of sensory blockade between two groups|
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The intraoperative hemodynamic parameters (HR and MAP) were maintained throughout surgery in both the groups and the difference was not statistically significant [Figure 2] and [Figure 3].
|Figure 3: Comparison of mean arterial pressure (MAP) between the two groups|
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Six patients (20%) in Group LF and three patients (10%) in Group LB developed nausea, although the difference was not statistically significant (P = 0.2801). None of the patients in either of the study groups had adverse effects such as bradycardia, hypotension, pruritus, or respiratory depression [Table 3].
| Discussion|| |
Intrathecal opioids with local anesthetics are nowadays the mainstay of spinal anesthesia. Apart from improving the duration and quality of analgesia, they also maintain hemodynamic stability by decreasing the dose requirements of local anesthetics. Common side effects of intrathecal opioids are drowsiness, nausea, vomiting, pruritus, and occasionally depression of ventilation. Fentanyl is a phenylpiperidine derivative synthetic opioid agonist, which acts as an agonist on mu and kappa opioid receptors and causes analgesia, euphoria, bradycardia, and sedation. As an analgesic, fentanyl is 75 to 125 times more potent than morphine. Due to its lipophilic nature, it has a rapid onset of action. Buprenorphine is an agonist-antagonist opioid that acts as an agonist at the mu receptor and as an antagonist at the kappa receptor. Its analgesic potency is approximately 30 times more than morphine. The high affinity of buprenorphine for opioid receptors is responsible for its prolonged duration of action. The intrathecal administration of bupivacaine with fentanyl or buprenorphine is routinely employed in lower limb surgeries. Recently, isobaric levobupivacaine has emerged as a safe alternative to hyperbaric bupivacaine in spinal anesthesia. Combination of intrathecal isobaric levobupivacaine with fentanyl or buprenorphine alone is also successfully used in recent times, although direct comparison is not available in the literature.,,
Levobupivacaine is claimed to be equipotent to racemic bupivacaine. The intrathecal dose of isobaric 0.5% levobupivacaine is 15–20 mg. The intrathecal dose of fentanyl is in the range of 10–30 mcg. It is associated with dose-dependent side effects of pruritus. The intrathecal dose of buprenorphine as an adjunct in spinal anesthesia ranges from 5 to 150 mcg but higher doses were associated with increased evidence of bradycardia and hypotension. Hence, we decided to use 10 mcg of fentanyl and 60 mcg of buprenorphine as an adjunct to 15 mg 0.5% isobaric levobupivacaine in our study. Singh et al. in their study have also used similar doses of fentanyl and buprenorphine as intrathecal adjuvants to ropivacaine.
We compared sensory and motor block characteristics as well as postoperative analgesia in both groups. We found the comparable onset of sensory block in both the study groups (P = 0.309). Pal et al. conducted a study to compare the effects of intrathecal buprenorphine and fentanyl as adjuvants to bupivacaine, where the onset of sensory block in both the groups was similar (P = 1.000) which correlates with our study. Gouroji et al. in their study compared the effects of intrathecal levobupivacaine versus levobupivacaine + fentanyl. Bhure et al. conducted a comparative study between intrathecal levobupivacaine, levobupivacaine + fentanyl, and levobupivacaine + dexmedetomidine. The onset time of sensory block in the LF group in the aforementioned studies is similar to our findings. Lee et al. conducted a study to compare the effects of levobupivacaine with levobupivacaine + fentanyl. They observed delayed onset of sensory block in Group LF compared to our study, which may be attributed to the fact that they have used a lower dose of levobupivacaine (2.3 mL). Ture et al. conducted a study comparing bupivacaine + buprenorphine and levobupivacaine + buprenorphine. The onset of sensory blockade in their Group LB was prolonged compared to values in our study.
The maximum level of sensory blockade was T6 in Group LF (n = 5) and Group LB (n = 2). The median level of maximum sensory block was T10 in both groups. The observations of our study correlate with the findings of studies by Lee et al., Attri et al. (levobupivacaine + fentanyl), Gouroji et al. for Group LF, and by Ture et al. for Group LB.
The mean duration of sensory block was significantly prolonged in Group LB than Group LF (P = 0.0000). Singh et al. (study of intrathecal buprenorphine and fentanyl with ropivacaine) and Pal et al. also observed increased duration of sensory block in the buprenorphine group which correlates with the findings of our study. In the study by Bhure et al., the duration of sensory block in the Fentanyl group was similar to our study. Gouroji et al. observed a shorter duration of sensory block in Group LF compared to our study even though they have used a higher dose of fentanyl. These variations may be attributed to the fact that they defined the duration of the sensory block as two-segment regression as opposed to regression to L1 in our study. Studies by Varma et al. (comparing levobupivacaine and levobupivacaine + fentanyl) and Attri et al. showed prolonged sensory blockade in Group LF compared to our findings as both these studies used 25 mcg of fentanyl and defined duration of the sensory block as the time from Spinal injection to regression to S1 level. Similarly, the duration of sensory blockade in the Buprenorphine group was less in our study compared to that observed by Ture et al. and Bhukya et al. The reason for this difference may be the use of a significantly higher dose of buprenorphine (2 mcg/kg versus 60 mcg) in these studies.
The onset of the motor blockade in our study was faster in Group LF compared to Group LB (P = 0.040). Pal et al. and Singh et al. also observed delayed onset of motor block in buprenorphine group than Fentanyl group. We observed a statistically comparable duration of the motor blockade in both groups (P = 1.000). The duration of motor block observed by Gouroji et al. in Group LF was lower which may be attributed to the use of a lower dose of levobupivacaine (2.5 mL) compared to our study (3 mL). The duration of motor block in our Buprenrphine group was comparable to the observations by Pal et al. and Ture et al.
The duration of analgesia was significantly prolonged in Group LB than in Group LF (P = 0.001). Our findings correlate with the studies by Pal et al., Singh et al., and Nehamangala et al.
We also compared the intraoperative hemodynamic stability in both groups. There was no statistically significant difference in the HR between the two groups at various time intervals. There were no incidences of bradycardia or hypotension in any of the study subjects at any given point of time during the study. Findings from our study correlate with those by Lee et al., Attri et al., and Varma et al.
In our study, six patients (20%) in Group LF and three patients (10%) in Group LB developed nausea. The difference was statistically not significant (P = 0.2801). None of the patients in our study had respiratory depression or pruritus. Our results are similar to observations by Gouroji et al., Singh et al., and Ture et al. Attri et al. observed pruritus in four patients in fentanyl group. This difference can be attributed to the use of a higher dose of fentanyl (25 mcg) in their study compared to our study (10 mcg). Hemodynamic stability as well as the absence of other major adverse effects such as respiratory depression and pruritus in the study subjects highlights the safety of both the study drug combinations.
| Conclusion|| |
Although combinations of 0.5% isobaric levobupivacaine (3 mL)–fentanyl (10 mcg) and 0.5% isobaric levobupivacaine (3 mL)–buprenorphine (60 mcg) show a good safety profile when administered intrathecally, combination of levobupivacaine–buprenorphine is superior in terms of prolonging sensory block and longer duration of postoperative analgesia. Hence, combination of levobupivacaine–buprenorphine can be preferred in surgeries of prolonged duration.
Ethical policy and institutional review board statement
This prospective randomized double-blind study was conducted after obtaining the written permission from the Institutional Ethics Committee for Research on Human Subjects of MGM Medical College, Aurangabad, India vide their letter no. MGM-ECRHS/2018/30 dated October 5, 2018.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]