|Year : 2011 | Volume
| Issue : 2 | Page : 190-195
Comparison of intrathecal bupivacaine-fentanyl and bupivacaine-butorphanol mixtures for lower limb orthopedic procedures
Binay Kumar, Aparna Williams, Dootika Liddle, Mary Verghese
Department of Anesthesia and Critical Care, Christian Medical College and Hospital, Ludhiana, Punjab, India
|Date of Web Publication||9-Apr-2012|
Department of Anesthesiology and Critical Care, Christian Medical College and Hospital, Ludhiana - 141 008, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Intrathecal use of butorphanol is less explored in human subjects.
Aims: To compare the safety and efficacy of anesthesia and analgesia of intrathecal bupivacaine-butorphanol mixture with intrathecal bupivacaine-fentanyl mixture.
Settings and Design: Tertiary level, teaching hospital. Prospective, randomized, double-blind study
Materials and Methods: Eighty patients aged above 18 years, of ASA physical status 1 or 2, undergoing lower limb orthopedic surgeries were randomly allocated to two groups of 40 patients each. Patients in group A and group B received intrathecal 2.5 ml of hyperbaric bupivacaine (0.5%), with 25 μg of fentanyl and 25 μg of butorphanol, respectively.
Statistical Analysis Used: Fisher's exact test and Chi square tests.
Results: The times required for onset of sensory and motor blockade were comparable among the two groups. Significantly slower block regression to S2 level was observed in the group receiving intrathecal butorphanol as compared to intrathecal fentanyl (P=0.0230). A higher number of patients in group A requested for rescue analgesia during the postoperative period than in group B (9 versus 2; P=0.0238). The average times to first request for rescue analgesia were 308.6±14.9 minutes and 365.9±12.3 minutes in group A and B, respectively (P=0.0254).
Conclusions: Both 25 μg fentanyl and 25 μg butorphanol given intrathecally along with 12.5 mg of hyperbaric bupivacaine provide effective anesthesia for lower limb surgeries. Intrathecal bupivacaine-butorphanol mixture provides longer duration of sensory blockade and superior analgesia than intrathecal fentanyl-bupivacaine mixture.
Keywords: Analgesia, anesthesia, bupivacaine, butorphanol, fentanyl, spinal
|How to cite this article:|
Kumar B, Williams A, Liddle D, Verghese M. Comparison of intrathecal bupivacaine-fentanyl and bupivacaine-butorphanol mixtures for lower limb orthopedic procedures. Anesth Essays Res 2011;5:190-5
|How to cite this URL:|
Kumar B, Williams A, Liddle D, Verghese M. Comparison of intrathecal bupivacaine-fentanyl and bupivacaine-butorphanol mixtures for lower limb orthopedic procedures. Anesth Essays Res [serial online] 2011 [cited 2019 Jun 17];5:190-5. Available from: http://www.aeronline.org/text.asp?2011/5/2/190/94775
| Introduction|| |
Neuraxial opioids are widely used in conjunction with local anesthetics (LA) as they permit the use of lower dose of LA while providing adequate anesthesia and analgesia.  Neuraxial opioids also allow prolonged analgesia in the postoperative period and faster recovery from spinal anesthesia.  Antinociceptive synergism between LA and intrathecal opioids has been demonstrated in various animal studies. 
The present study was undertaken to compare the safety and efficacy of anesthesia and analgesia of intrathecal bupivacaine-butorphanol mixture with intrathecal bupivacaine-fentanyl mixture for lower limb orthopedic procedures. This study was conducted as only a limited number of studies have explored the use of intrathecal butorphanol in human subjects previously.
Butorphanol is a lipophilic opioid agonist-antagonist analgesic with a published affinity for opioid receptors in vitro of 1:4:25 (mu: delta: kappa).  Abboud et al. have reported a dose-dependent increase in the duration of analgesia provided by epidural butorphanol for relief of post-cesarean section pain.  Fentanyl, a highly lipid soluble, pure μ-agonist opioid with rapid onset and short duration of action, has been used with various local anesthetics for a wide variety of surgical procedures. ,
| Materials and Methods|| |
This prospective, randomized, double blind study was conducted after approval from the institutional ethics committee and informed, written consent of patients. Eighty patients, aged 23-75 years, belonging to ASA physical status 1 or 2 and scheduled for elective, lower limb orthopedic surgeries were randomized into two groups using random numbers generated by the computer. Patients in group A (Gp A) received 2.5 ml of 0.5% hyperbaric bupivacaine (Sensorcaine,TM, Astra Zeneca, Bellary road, Karnataka, India) with 0.5 ml (containing 25 μg fentanyl) (Fendrop, TM, Sun Pharmaceuticals, Halol, Gujrat, India); a total volume of 3 ml intrathecally. The butorphanol (Butodol, TM, Neon, Andheri (E), Maharashtra, India) was diluted using distilled sterile water to obtain 25 μg in 0.5 ml. The 25 μg of butorphanol was then added to 2.5 ml of 0.5% hyperbaric bupivacaine to make a total volume of 3 ml to be given intrathecally to patients in group B (Gp B).
All patients underwent a complete general physical examination and systemic examination and were explained the linear visual analogue scale (LVAS) scoring system for pain during the pre anesthetic check-up. The LVAS used an 11-cm line where 0 denoted "no pain" while 10 denoted "worst pain imaginable".
Patients in whom spinal anesthesia or the study drugs were contraindicated were excluded from the study. Patients with neurological disease, spinal deformities, local skin infection or mental disorders; those who were morbidly obese, hemodynamically unstable or had coagulation disorders, or patients with liver disease, impaired renal functions, ASA Physical status >2 or a history of opioid dependence were also excluded from the study.
Patients were kept fasting for 6 hours to solids and 2 hours to clear fluids preoperatively and received no pre medication. In the operation theatre, an intravenous line was established. The intrathecal drugs were prepared by a trained anesthesia nurse beforehand to maintain the blinding process. Baseline heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR) and peripheral arterial oxygen saturation (SpO 2 ) were recorded for all subjects. All patients received 10 ml/kg of lactated ringer's solution as preload within 20- 30 minutes. The primary investigator entered the operation theatre after this period and was therefore blinded to the patient allocation. All spinal blocks were given by the same anesthesiologist. Subarachnoid block was performed under strict aseptic conditions in the lateral position at the level of L 3-4 or L 4-5 inter vertebral space using 25 G Quincke's spinal needles. The midline approach was used to perform the spinal blocks after infiltrating the skin with 1 ml of 2% Lidocaine. The test drug was injected over 15 seconds. Following the subarachnoid block, the patient was put in supine position.
Intraoperatively, HR, SBP, DBP, RR and SpO 2 were recorded at 2 minutes (min) intervals for the first 20 min from the time of injection of spinal solution and there after every 15 min. for the complete period of surgery. This data was recorded by the attending anesthesiologist and the primary investigator, who were unaware of the patient allocation. Hypotension (MAP <70 mmHg) was treated with fluid boluses and 6 mg intravenous (IV) boluses of ephedrine, while bradycardia (HR <50bpm) was treated with 0.6 mg IV atropine. Respiratory depression was defined as a respiratory rate <8 breaths/min or a SpO 2 of <90% on room air. All patients were given supplemental O 2 via face mask at 6 l/min if the SpO 2 decreased below 90%.
The highest level of sensory block was determined in the midclavicular line bilaterally, by pinprick test using a 20-G hypodermic needle every 2 min till the level had stabilized for four consecutive tests. The highest level of sensory block and the time taken to attain it from the time of the intrathecal injection were recorded. Further sensory testing was performed at 20-min intervals till the recovery of S2 dermatome. Motor block was assessed using the modified Bromage scale;  (grade 0 = no motor block; grade 1 = inability to raise extended legs, able to move knees and feet; grade 2 = inability to raise extended leg and move knee, able to move feet and grade 3 = complete motor block of the lower limbs) till achievement of the highest sensory level; at the end of the surgery and then at 30 min intervals till the patient had no motor blockade.
Side effects such as hypotension, bradycardia, nausea, vomiting, sedation, pruritis, shivering and respiratory depression were recorded. The time to voiding was also recorded. The quality of postoperative analgesia was assessed using LVAS at 15 min, 30 min and thereafter every 30 min, till 2 hours postoperatively; and then every hour, till 4 hours postoperative duration. The time of first request of rescue analgesia was recorded. Patients reporting an LVAS score of ≥4 were treated with 75 mg diclofenac IV infusion in 100 ml of 0.9% saline, as rescue analgesic.
On the third postoperative day the patients were interviewed regarding complications of spinal e.g., backache, transient neurological symptoms (TNS) or postdural puncture headache (PDPH). PDPH was defined as headache that was mainly occipital or frontal, aggravated by erect or sitting posture, relieved on lying flat, and increased on coughing, sneezing or straining. TNS were defined as any pain or dysesthesia in the back, buttocks and legs or pain radiating to the lower limbs after recovery from spinal anesthesia, and which resolved within 72 hours. Thereafter, the patients were followed up daily till their discharge from the hospital to recognize any other complications of the subarachnoid block.
Using the Priori power analysis with α of 0.05, anticipated effect size of 0.8 and a desired statistical power level of 0.9, a minimum sample size of 34 subjects was required per group for a two tailed hypothesis. We decided to recruit 40 patients to each group to make up for any dropouts from the study groups.
The data were compiled using Microsoft excel (2007) and analyzed using paired/unpaired t tests and Fisher's exact tests on the Epi Info software (version 8.0) to assess the statistical difference between the groups. A P value of <0.05 was accepted as statistically significant.
| Results|| |
The two groups were comparable with regards to age, gender, weight, height and duration of surgery [Table 1]. The mean baseline values of HR, SBP, DBP, RR and SpO 2 were comparable among the groups.
The characteristics of sensory block in the two groups are depicted in [Table 2]. The median highest sensory level achieved and the times to reach peak sensory level were comparable among the two groups. Significantly slower block regression to S 2 level was observed in the group receiving butorphanol as compared to fentanyl (P=0.0230).
The characteristics of motor blockade achieved in the two groups are listed in [Table 3]. The time of onset of maximum motor blockade (P=0.1288) and time to reach grade 1 motor blockade (P=0.1080) were similar among the two groups.
The postoperative LVAS pain scores are presented in [Table 4]. Patients receiving butorphanol had lower LVAS pain scores at all observed times than patients who received fentanyl, although this difference in LVAS scores reached a statistical significance only at 1-hour postoperative duration (P=0.0260). A higher number of patients in the fentanyl group requested for rescue analgesia during the postoperative study period than the butorphanol group (9 versus 2; P=0.0238) [Table 5]. The patients in the fentanyl group requested rescue analgesia earlier than patients in the butorphanol group as the average times to first request for rescue analgesia were 308.6±14.9 and 365.9±12.3 minutes, respectively (P=0.0254).
The complications observed during the study are listed in [Table 5]. Seven patients in the fentanyl-treated group and two patients in the butorphanol-treated group had hypotension in the peri-operative period (P=0.0771). The intraoperative systolic blood pressures and diastolic blood pressures for the study groups are presented in [Figure 1] and [Figure 2] respectively.
|Figure 1: Comparison of intraoperative systolic blood pressures among the study groups|
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|Figure 2: Comparison of intraoperative diastolic blood pressures among the study groups|
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Bradycardia, responsive to a single dose of intravenous atropine was seen in two patients in the group receiving fentanyl as compared to none in the butorphanol group (P=0.2468). The intraoperative heart rates for the study groups are presented in [Figure 3].
|Figure 3: Comparison of intraoperative heart rates among the study groups|
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Pruritis was observed in five patients receiving fentanyl as compared to none of the patients who received butorphanol (P=0.0273). Although six patients in the butorphanol group had sedation compared to none in the fentanyl group (P=0.0127); none of the patients developed respiratory depression. [Figure 4] depicts the intraoperative respiratory rates in the two study groups.
|Figure 4: Comparison of intraoperative respiratory rates among the study groups|
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Comparable times to voiding were observed in both the groups (172.6±4.5 min in group A and 188.7±3.8 min in group B; [P=0]). Four patients in the fentanyl group and three in the butorphanol group required urinary catheterisation due to difficulty in voiding. Nausea; vomiting, PDPH and TNS were not reported by any of the patients.
| Discussion|| |
The principal findings of this study are that intrathecal butorphanol-bupivacaine mixture provides longer duration of sensory blockade and superior analgesia (with lesser requirement for rescue analgesia) as compared to intrathecal fentanyl-bupivacaine mixture.
The use of opioids in conjunction with local anesthetic for spinal anesthesia has been associated with decreased pain scores and reduced analgesic requirement in the post-operative period. , Results of previous studies have demonstrated that intrathecal opioids not only enhance analgesia when added to subtherapeutic doses of local anesthetics but also do not prolong recovery. ,,
In our study, both fentanyl and butorphanol along with bupivacaine, provided adequate anesthesia and analgesia; but significantly lesser analgesic requirement was observed in the group receiving intrathecal butorphanol and bupivacaine mixture compared to intrathecal fentanyl and bupivacaine mixture. The time for first request of analgesia with the use of intrathecal butorphanol and fentanyl, in conjunction with bupivacaine, in our study was about 6 hours and 5 hours respectively from the time of spinal injection. Kim et al. have reported the duration of analgesia of approximately 7 hours after the use of 4 mg bupivacaine with 25 μ fentanyl for TURP.  Earlier studies report the duration of analgesia with intrathecal fentanyl ranging from one to four hours.  Singh V et al., have also reported that lesser number of patients receiving intrathecal butorphanol requested for rescue analgesia as compared to those receiving intrathecal fentanyl.  Studies comparing intravenous butorphanol and fentanyl have reported the equianalgesic doses as 1 μg/kg and 20 μg/kg for fentanyl and butorphanol, respectively.  We studied the 25 μg dose of intrathecal fentanyl and butorphanol based on earlier studies. 
The results of our study are consistent with experimental evidence of synergistic interaction between spinal opioids and local anesthetics, which are characterized by enhanced somatic analgesia without effect on the degree or level of the local anesthetic induced sympathetic or motor blockade. , The synergism between intrathecal opioids in addition to local anesthetics is due to the drugs' separate mechanism of action; blockade of Na + channel by local anesthetics  and voltage-gated Ca ++ channels with opioids. ,
The combination of opioids with LA allows for a reduction in doses of the LA, thus lessening the likelihood of side effects. , A low incidence of side effects was observed in our study. Seven patients (17.5%) in the fentanyl treated group and two patients (5%) in the butorphanol-treated group had hypotension in our study requiring treatment with small doses of intravenous ephedrine (6 mg in 7 and 12 mg in 2 patients) in addition to crystalloid bolus. Neuraxial administration of opioids has been reported to be associated with hypotension.  Earlier studies comparing 25 μg intrathecal fentanyl and butorphanol with hyperbaric bupivacaine, have reported the instance of hypotension as 20% in the fentanyl group and 17% in the butorphanol group. 
However, animal studies have reported that fentanyl does not potentiate the effect of Bupivacaine on efferent sympathetic pathways.  Furthermore, the addition of fentanyl (20-25 μg) to low-dose bupivacaine (4 mg) has been reported to increase the perioperative quality of spinal blocks with fewer cardiovascular changes in elderly patients. 
Five patients (12.5%) in the group receiving fentanyl- bupivacaine had pruritis compared with none in the group receiving butorphanol-bupivacaine. The pruritis was mild in nature and did not require any treatment. Pruritis is the commonest side effect of intrathecal opioids.  In earlier studies on spinal anesthesia for ambulatory knee arthroscopy, the combination of bupivacaine with fentanyl was associated with an instance of pruritis ranging from 48 to 75% compared with the groups receiving bupivacaine alone.  Ackerman et al.  have also reported that opioids that stimulated κ-receptors following epidural administration exhibited significantly less pruritis than pure μ-receptor opioids administered similarly. Furthermore, investigators have reported that continuous epidural butorphanol relieves pruritis associated with epidural morphine infusions in children. 
Although six patients had sedation in the group receiving butorphanol-bupivacaine, as compared with none in the group receiving fentanyl; none of them had respiratory depression. Sedation is a reported side effect of neuraxially administered butorphanol.  Varassi et al. have reported that bupivacaine 15 mg along with 25-μg fentanyl did not cause respiratory depression in elderly patients. 
Seven patients were catheterised during the postoperative period due to difficulty in voiding, although the average times to voiding were comparable among both the study groups. Previous studies have reported that intrathecal bupivacaine is associated with a clinically significant disturbance of bladder function and spontaneous voiding may not be expected until the sensory blockade has regressed to the S3 level.  None of the patients in the study experienced nausea or vomiting as we promptly treated all episodes of hypotension. None of the patients reported PDPH or TNS.
The obvious limitation of our study includes the absence of a control group (in which patients would have received 2.5 ml of hyperbaric bupivacaine along with 0.5 ml of saline intrathecally). The inclusion of a control group would have further supported our findings. We also recognize the fact that the wide variability in the age of the patients included in the study is a confounding factor in relation to perception of pain as pain perception varies for various age groups. We studied postoperative analgesia in the subjects for duration of 4 hours only and did not record the number of doses and the total dose of rescue analgesic required to relieve pain. Further investigation can be aimed at finding the minimal possible doses of intrathecal fentanyl and butorphanol in conjunction with hyperbaric bupivacaine that will provide adequate anesthesia and analgesia for lower limb surgeries.
In conclusion, both 25-μg fentanyl and 25-μg butorphanol given intrathecally with 12.5 mg of hyperbaric bupivacaine provide effective and safe anesthesia for lower limb surgeries with minor side effects. Intrathecal bupivacaine-butorphanol mixture provides longer duration of sensory blockade and better quality of analgesia than intrathecal fentanyl-bupivacaine mixture.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]