Intrathecal Butorphanol Research Articles

Duration of postoperative analgesia with Nalbuphine vs Butorphanol as an adjunct to spinal anesthesia for lower limb orthopedic surgeries: A randomized double-blind active control trial.

Background and Aims:Nalbuphine as well as butorphanol as adjuvant to intrathecal bupivacaine have been studied in comparison to bupivacaine alone. Both are kappa receptor agonist and have never been compared for its efficacy in terms of postoperative analgesia. The aim of this study was to evaluate duration of postoperative analgesia as well as intraoperative block characteristics using intrathecal nalbuphine hydrochloride (800 μg) or butorphanol (25 μg) as adjuvant to hyperbaric bupivacaine (12.5 mg) in lower limb fracture femur surgeries as compared to active control, that is, saline and bupivacaine.Material and Methods:This prospective, randomized, double-blind, active control study was conducted on 90 adult patients of either sex belonging to ASA grade I/II, aged 18–70 years, being operated for fracture femur surgeries in tertiary care hospital of North India. Patients were randomly divided into 3 groups (n = 30) Group A: received 0.5% hyperbaric bupivacaine 12.5 mg with 800 μg nalbuphine. Group B: Received 0.5% hyperbaric bupivacaine 12.5 mg with 25 μg butorphanol. Group C: Received 0.5% hyperbaric bupivacaine 12.5 mg with normal saline. Total volume injected was 3.0 ml. Duration of analgesia, mean VAS scores, requirement of rescue analgesia in 24 h along with intraoperative sensory or motor characteristics of block and hemodynamic parameters were studied. Statistical analysis was done using ANOVA with post-hoc Tukey test, Student’s t-test and Chi-Square test.Results:Demographic profile was comparable among all the three groups. Mean duration of postoperative analgesia was 348.33 ± 66.96, 156.17 ± 43.9 and 110.36 ± 29.18 min in group A, B, and C, respectively (P = 0.006). Total doses of rescue analgesia were least in group A (32), followed by group B (42) and group C (64), respectively (P = 0.001). Group A had significantly earlier onset of sensory action (P = 0.03) as compared to group B and C. There was significant difference in sensory (P = 0.08) and motor duration (P = 0.04) among all the three groups. However, onset of motor block, haemodynamic profile and side effects were comparable among groups A, B, and C (P > 0.05).Conclusion:Addition of 800 μg nalbuphine and 25 μg butorphanol as adjuvant to intrathecal bupivacaine has better outcome as compared to active placebo group. But intrathecal nalbuphine was more effective compared to intrathecal butorphanol in terms of prolonging postoperative analgesia, reducing rescue analgesic doses and onset of sensory block. However, hemodynamic profile and side effects were comparable among all groups.

Comparison between intrathecal nalbuphine and butorphanol as adjuvants to isobaric ropivacaine in elective lower limb orthopedic surgeries: A prospective, randomized, double blind study

Background: Intrathecal ropivacaine is now routinely used for lower limb surgery. Adjuvants e.g. fentanyl, dexmedetomidine or morphine etc. are commonly used to prolong the intraoperative anesthesia or postoperative analgesia. The available literature lacks information on use of butorphanol and nalbuphine as adjuvants with 0.75% isobaric ropivacaine. We aimed to compare nalbuphine and butorphanol as adjuvant with isobaric ropivacaine in lower limb orthopedic surgeries.
 Methodology: After institutional ethical committee approval and informed written consent, a total of 108 patients of ages between 18 to 65 y, of either sex, American Society of Anesthesiologists (ASA) grade ӏ & ӏӏ, scheduled for elective lower limb orthopedic surgeries, were enrolled and randomly allocated into two groups: Group RN; to receive isobaric ropivacaine (0.75%, 7.5 mg/ml) 2.5 ml plus nalbuphine 500 µg (0.5 ml), and Group RB; to receive isobaric ropivacaine 2.5 ml plus butorphanol 100 µg (0.5 ml) intrathecally. Primary outcome measure was the duration of sensory‑motor blockade from the time of intrathecal drug administration. Statistical analysis was performed by using t-test and chi-square test as applicable. A p < 0.05 was considered as significant.
 Results: Duration of sensory (p < 0.001) and motor blockade (p = 0.02) was significantly prolonged in nalbuphine group than butorphanol group. Onset of blockade was earlier in nalbuphine group. Duration of motor block and sensory analgesia was prolonged in group RN (p < 0.001). Perioperative hemodynamic parameters and the observed side effects including bradycardia, hypotension, nausea and vomiting, sedation and shivering were comparable between the two groups (p = 0.77).
 Conclusion: Intrathecal nalbuphine produces prolonged motor blockade as well as postoperative analgesia than intrathecal butorphanol when used as adjuvants to isobaric 0.75% ropivacaine.
 Citation: Nirmal A, Singh Y, Mathur SK, Patel S. Comparison between intrathecal nalbuphine and butorphanol as adjuvants to isobaric ropivacaine in elective lower limb orthopedic surgeries: A prospective, randomized, double blind study. Anaesth pain & intensive care 2019;23(4)__
 Received: 22 August 2019; Reviewed: 8, 9 October 2019; 6, 7 November 2019; Revised: 18 November 2019; Reviewed: 19 November 2019; Accepted: 20 November 2019

Intrathecal Butorphanol: An Effective Option for Post Operative Pain Relief in Caesarean Patients

Intrathecal Butorphanol: An Effective Option for Post Operative Pain Relief in Caesarean Patients

A comparative study to assess the effect of intrathecal bupivacaine with morphine or butorphanol on post-operative pain relief following abdominal and vaginal hysterectomy

Background: Post-operative pain management can be challenging. Objectives: To compare the efficiency of morphine with that of butorphanol in controlling the postoperative pain relief. Methods: This double-blind randomized clinical trial was performed on 75 consecutive patients. Intrathecal 3ml hyperbaric bupivacaine mixed with morphine (200 microgm-0.25ml); or mixed with butorphanol (200 microgm-0.25ml); or mixed with normal saline 0.25ml was administered to alternate groups (25 patients in each group), for postoperative pain relief after abdominal and vaginal hysterectomy. They were monitored for pain relief in the recovery and gynaecological ward for 24 hours. If the patient had any complications like nausea, vomiting, itching and urinary retention were recorded. Results: Time for two segment regression of sensory level in patients receiving intrathecal morphine (Group-M), was 114.0±12.2 min., intrathecal butorphanol (Group- B) was 96.0+24.4 min and normal saline (Group- N) was 104.4 ± 18.5min. Duration of pain relief after subarachonoid block In Group-M was 492.0 ± 153.2min, in Group- B 311.20 ±58.7min and in Group-N it was 299.4 ± 72.7min. Two patients (8%) in Group-M had nausea, vomiting and itching but none in other groups. Urinary retention occurred in 3 patients (12%), in Group- M, whereas the same was found in 2 patients (8%) and 1 patient (4%) of Group-B and N respectively. Conclusion: Intrathecal morphine provided prolonged and better analgesic effect after abdominal and vaginal hysterectomy than butorphanol, though there were some side effects like nausea, vomiting, itching and urinary retention which were graded by the patients as clinically not significant. DOI: http://dx.doi.org/10.3126/hren.v11i3.9640 Health Renaissance 2013;11(3):246-249

A Comparative Study Of Butorphanol As An Adjunct To Bupivacaine In Comparison To Bupivacaine Alone.

Neuraxial opioids are widely used in conjunction with local anaesthetics (LA) as they permit the use of lower dose of LA while providing adequate anaesthesia and analgesia. Neuraxial opioids also allow prolonged analgesia in the postoperative period and faster recovery from spinal anaesthesia. 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 anaesthesia and hemodynamic stability of different doses of intrathecal bupivacaine-butorphanol mixture with intrathecal bupivacaine alone for lower abdominal & lower limb surgery. 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). Studies have reported a dose-dependent increase in the duration of analgesia provided by epidural butorphanol for relief of post-caesarean section pain. I. Methods Fourty six patients of ASA grade I and II between 18-58yrs of age of either sex, scheduled for elective lower abdominal & lower limb surgical procedure were included The study protocol was approved by Institutional Ethical Committee and written informed consent was obtained from all patients. The pre-anaesthetic check-up included a detailed medical and surgical history, and any previous anaesthetic exposure with its outcome. General examination includes general condition, built, weight, pulse rate, blood pressure, respiratory rate, and presence of cyanosis, anaemia, clubbing, jaundice or edema. A careful thorough systemic examination was done to rule out any cardiovascular, respiratory, gastrointestinal and neurological or any other systemic illness.Routine biochemistry investigation included haemoglobin, total leucocyte count, differential leucocyte count, blood sugar, blood urea, and serum creatinine, were done in all patients. ECG and X-Ray Chest were done in patients where indicated and in those over 40 years of age along with other relevant investigation. After taking detailed history and thorough clinical examination, the patients were excluded from the study on the basis of below mentioned criteria: Patients with systemic hypertension, hepatic dysfunction, renal dysfunction, endocrine dysfunction, cardiac dysfunction, morbid obesity (body weight more than 20% of the ideal body weight),Other exclusion criteria were patients with known drug hypersensitivity, those on antihypertensive medication or antidepressant

Comparison of intrathecal bupivacaine-fentanyl and bupivacaine-butorphanol mixtures for lower limb orthopedic procedures.

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 studyMaterials 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 testsResults: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.

Supersensitivity of spinal opioid receptors to antagonists in intrathecal butorphanol and morphine dependence

The purpose of this investigation was to evaluate changes in the sensitivity of spinal opioid receptors to selective antagonists in rats rendered dependent on intrathecal (i.t.) butorphanol and morphine. Using quantitative autoradiography, competitive binding assays with selective opioid antagonists were performed in the spinal cord sections of i.t. Butorphanol- and morphine-dependent rats in which withdrawal was precipitated by i.t. Naloxone. In butorphanol-dependent rats, the spinal κ-opioid receptor developed a greater degree of antagonist supersensitivity than the spinal δ- and μ-opioid receptors did. In contrast, the spinal μ-opioid receptor became more sensitive than the δ-opioid receptor in morphine-dependent rats. These results indicate that differential supersensitivity of spinal opioid receptors was induced after chronic i.t. infusions of butorphanol and morphine.

Visceral analgesic tolerance to intrathecal butorphanol in rats.

Recent experimental data suggest that intrathecal (it) kappa-opioid agonists produce profound visceral analgesia. This study investigated the development of visceral analgesic tolerance to it butorphanol, a potent kappa-agonist that has fewer side effects than commonly used it opioids. Understanding of this tolerance could make it butorphanol more effective in treating chronic visceral pain. This was a randomized, controlled animal study involving 80 Sprague-Dawley rats. Rats implanted with lumbar it catheters were infused either with it saline or butorphanol (52 nmol.hr-1) for 96 hr. Six hours afterwards, each rat was challenged once with one of the differing it butorphanol doses to construct dose-response curves. Visceral analgesia was evaluated by the abdominal writhing responses to the acetic acid injected intraperitoneally. The time of the first writhe and the total number of writhes were recorded. For both the saline- and butorphanol-infused groups, a higher challenge dose of it butorphanol produced longer time for the first writhe to occur (P < 0.01, one-way ANOVA), and fewer writhes occurring within 30 min (P < 0.01, one-way ANOVA). However, the dose response curves of the butorphanol-infused groups were shifted rightward (P < 0.001, partial F test). The challenge doses of it butorphanol produced dose-dependent visceral analgesia in both the saline- and butorphanol-infused groups, confirming its efficacy. The butorphanol-infused groups showed dose-response shifts, demonstrating the development of tolerance to this visceral analgesia.

Subtype Opioid Receptor Involvement in Development of Dependence on Intrathecal Butorphanol vs. Morphine

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Relative Involvement of Spinal Opioid Receptors in Physical Dependence on Intrathecal Butorphanol and Morphine

The present study was carried out to investigate the relative involvement of spinal opioid receptors in the development of physical dependence on intrathecal (IT) butorphanol in comparison with IT morphine. Dependence was induced by continuous IT infusion of butorphanol (52 nmol/h) and morphine (26 nmol/h) for 4 days in male Sprague–Dawley rats. Naloxone, CTOP, naltrindole, and nor-binaltorphimine (nor-BNI) were administered IT to precipitate behavioral signs of withdrawal. Administration of IT naloxone produced a significantly greater increase in the profile of withdrawal signs in IT morphine dependence than that in IT butorphanol dependence. An IT nor-BNI challenge elicits behavioral signs of withdrawal only in rats dependent on IT butorphanol, but not in rats dependent on IT morphine. CTOP administered IT precipitated withdrawal signs in IT morphine dependence that were greater than that in IT butorphanol dependence. An IT treatment with naltrindole produced equivalent signs of withdrawal in both IT butorphanol- and morphine-dependent rats. These results suggest that continuous IT butorphanol results in the development of less physical dependence than that of IT morphine. Spinal κ- rather than δ- and μ-opioid receptors play a major role in the development of IT butorphanol dependence, whereas spinal μ-opioid receptors play a more important role than δ-opioid receptors in IT morphine dependence.

Physical Dependence Induced by Intrathecal Butorphanol Versus Morphine in Rats

Physical Dependence Induced by Intrathecal Butorphanol Versus Morphine in Rats

Differential Involvement of Opioid Receptors in Intrathecal Butorphanol-Induced Analgesia: Compared to Morphine

The present experiments were performed to investigate the differential involvement of the opioid receptor subtypes in the antinociception of intrathecal (IT) butorphanol compared to IT morphine. A single dose (26 nmol) of IT nor-binaltorphimine (nor-BNI), β-funaltrexamine (β-FNA), and naltrindole (NTI) demonstrated a significant attenuation in the overall antinociception of IT butorphanol (52 nmol) or IT morphine (26 nmol). However, IT butorphanol elicits thermal antinociceptive effect through κ > δ ⩾ μ, whereas morphine acts on μ > δ >> κ. These results indicate that the antinociceptive effect of both IT butorphanol and IT morphine are mediated through μ, δ, and κ opioid receptors in different relative orders.

Decreased paralysis and better motor coordination with microspinal versus PE10 intrathecal catheters in pain study rats.

We compared the standard PE10 catheter to a smaller microspinal catheter for intrathecal (IT) catheterization in rats. The PE10 or microspinal catheter was implanted in the lumbar subarachnoid space through the atlantooccipital membrane in rats (21 each group). Surviving rats without paralysis were tested on a rota-rod treadmill for motor function on Postoperative Days (POD) 3-6. Different doses of IT butorphanol were injected to demonstrate the functionality of the catheters by measuring tail-flick antinociception. Methylene blue was injected IT immediately before the spinal necropsy in each rat to identify the catheter tip location. For PE10 and microspinal catheters, the immediate death rate after the catheter implantation was 4 of 21 and 3 of 21 (no significant difference); paralysis rate was 8 of 21 and 2 of 21 (P < 0.05), and motor coordination recovery on POD6 was 67% and 91% (P < 0.01), respectively. Rats in both groups showed a dose-dependent response to IT butorphanol. Intrathecal methylene blue stained the lumbar spinal cord but not the surrounding tissue in both groups. Therefore, the microspinal catheter is better than the PE10 for IT catheterization in rats because it causes less paralysis and provides faster recovery of motor function.