|Year : 2020 | Volume
| Issue : 4 | Page : 161-165
Comparison of nalbuphine versus fentanyl as an adjuvant to 0.75% isobaric ropivacaine in subarachnoid block for orthopedic surgery of lower limbs: A randomized, double-blind study
Vivek Mavaliya1, Babita2, ML Tak1, Bhupendra Singh1, Satveer Singh Gurjar3
1 Department of Anaesthesiology, Dr. S N Medical College and Attached Hospitals, Jodhpur, Rajasthan, India
2 Department of Anaesthesiology, Divisional Railway Hospital, Jodhpur, Rajasthan, India
3 Department of Anaesthesiology, SMS Medical College and Attached Hospitals, Jaipur, Rajasthan, India
|Date of Submission||22-Jun-2020|
|Date of Decision||16-Jul-2020|
|Date of Acceptance||05-Aug-2020|
|Date of Web Publication||05-Oct-2020|
Dr. Satveer Singh Gurjar
218-A, Pashupatinath Nagar, Pratapnagar, Jaipur - 302 033, Rajasthan
Source of Support: None, Conflict of Interest: None
Background: Ropivacaine is an effective and safe alternative local anesthetic for subarachnoid block with a lesser duration of motor blockade and less neuro-cardiotoxicity. While fentanyl is commonly used as an adjuvant, nalbuphine recently got popular by its μ-attenuation and k-accentuation effects. We compared the efficacy of intrathecal fentanyl versus nalbuphine as an adjuvant to ropivacaine in subarachnoid block. Materials and Methods: In this prospective, randomized, double-blind study, seventy adult patients who were posted for elective lower limb orthopedic surgeries were randomly allocated to two groups. Group F received 22.5 mg of 0.75% isobaric ropivacaine with 25 μg fentanyl, and Group N received 22.5 mg of 0.75% isobaric ropivacaine with 1 mg nalbuphine intrathecally. Hemodynamics, onset, block duration, peak sensory level, two-segment regression time, and adverse effects such as nausea, vomiting, pruritus, sedation, hypotension, and bradycardia were studied. P < 0.05 was considered statistically significant. Results: Both groups achieved the target sensory level of T10. Time for onset of sensory and motor blockade, time to achieve peak sensory level, and motor block duration were statistically comparable in both groups. The duration of the sensory block was 254.45 ± 20.69 min in Group F and 297.4 ± 19.0 min in Group N (P < 0.001). The duration of analgesia was 275.6 ± 18.76 min in Group F and 318.2 ± 14.14 min in Group N (P < 0.001). Conclusions: Nalbuphine prolongs the duration of the sensory block along with the duration of postoperative analgesia in comparison to fentanyl as an intrathecal adjuvant to 0.75% isobaric ropivacaine for subarachnoid block.
Keywords: Fentanyl, nalbuphine, postoperative analgesia, ropivacaine, subarachnoid block
|How to cite this article:|
Mavaliya V, Babita, Tak M L, Singh B, Gurjar SS. Comparison of nalbuphine versus fentanyl as an adjuvant to 0.75% isobaric ropivacaine in subarachnoid block for orthopedic surgery of lower limbs: A randomized, double-blind study. Bali J Anaesthesiol 2020;4:161-5
|How to cite this URL:|
Mavaliya V, Babita, Tak M L, Singh B, Gurjar SS. Comparison of nalbuphine versus fentanyl as an adjuvant to 0.75% isobaric ropivacaine in subarachnoid block for orthopedic surgery of lower limbs: A randomized, double-blind study. Bali J Anaesthesiol [serial online] 2020 [cited 2021 Jan 24];4:161-5. Available from: https://www.bjoaonline.com/text.asp?2020/4/4/161/299868
| Introduction|| |
Subarachnoid block is a safe, cost-effective, and easy to perform technique which provides rapid onset and reliable anesthesia along with low-risk of infection but has the drawbacks of shorter duration of block and short postoperative analgesia. Ropivacaine having less cardiac and central nervous system (CNS) toxicity is structurally similar to bupivacaine used as pure S-enantiomer rather than a racemic mixture. Neuraxial opioids are synergistic with local anesthetics (LA) and prolong spinal anesthesia and postoperative analgesia. The addition of opioids such as sufentanil/fentanyl improved and prolonged spinal anesthesia duration and reduced the amount of LA required to perform a sufficient dermatome spread and block intensity.
A lipophilic opioid like fentanyl (μ-agonist) became the adjuvant of choice because of its potency, rapid onset, and short duration of action with a lower incidence of respiratory depression. Fentanyl is commonly used as an intrathecal adjuvant in doses of 10–25 mcg. Central neuraxial opioids are known for their side effects, such as pruritus, urinary retention, and respiratory depression.
Nalbuphine, a mixed opioid κ-agonist with μ-antagonist, has a potential to attenuate the μ-opioid side effect (nausea, emesis, pruritus, constipation, undesirable sedation, respiratory depression and the development of tolerance/dependence) and enhance the analgesia by κ-opioid receptors. Usual doses of nalbuphine range from 0.8 to 1.6 mg as an intrathecal adjuvant to LA in a subarachnoid block. Therefore, this prospective, randomized, double-blind study was designed to assess the duration of analgesia with an observation of the hemodynamic stability and CNS safety profile of nalbuphine in comparison to fentanyl when used as an adjuvant to intrathecal ropivacaine in lower limb orthopedic surgeries under subarachnoid block. We also compared the properties of sensory and motor block achieved by both the drugs and looked for adverse effects, if any.
| Materials and Methods|| |
This hospital-based prospective, double-blind, randomized study was conducted after approval of the institutional ethical committee (No. SNMC/IEC/2019/509-511, dated August 6, 2019) at the Department of Anaesthesiology and Critical Care of Dr. S. N. Medical College, Jodhpur. Seventy patients were grouped into two groups (35 each) after randomization done by computer-generated random numbers sequence using Research Randomizer (version 4.0) [Computer Software] developed by Urbaniak G.C. & Plous, S. (2013). Software developers based in Lancaster, Pennsylvania, USA.
Group F received 22.5 mg (3 ml) of 0.75% isobaric ropivacaine and 25 μg fentanyl (0.5 ml) and Group N received 22.5 mg (3 ml) of 0.75% isobaric ropivacaine and 1 mg nalbuphine (0.1 ml nalbuphine and 0.4 ml normal saline) intrathecal. The total study drug mixture volume given was 3.5 ml for each group. The sample size was based on the results of the duration of analgesia in a previous study.,
For proper double-blinding, the drug was prepared in a 5 ml syringe in equal volume by an anesthesiologist who was different from the staff who performed the subarachnoid block and who assessed the block properties and the hemodynamics. All adult patients with ASA physical status I or II of either sex, 18–60 years aged, 48–90 kg weight, 151–180 cm height, and body mass index (BMI) between 20 and 35 kg/m2, posted for elective lower limb orthopedic surgery of 1–1.5 h duration under spinal anesthesia were included in the study. The preanesthetic evaluation was carried out 1 day before a detailed history and examination. Basic demographic data such as age, sex, height, and weight were recorded, and routine investigations were checked as per institutional guidelines from all the patients.
We excluded the patients with known hypersensitivity to LA, infection at the injection site, history of bleeding disorders or on anticoagulants, pregnancy, anatomical abnormality, and any comorbid condition such as preexisting peripheral neuropathy or neurological deficit, cerebrovascular accidents, endocrine, severe hepatic and renal dysfunction, chronic obstructive pulmonary disease, diabetes, sepsis, heart blocks, or dysrhythmias. Patients on tranquilizers, hypnotics, sedatives, and other psychotropic drugs and drug addicts to opium or alcohol were also excluded from the study. Patients were explained in detail about the anesthesia procedure, drugs, and visual analog scale (VAS) for pain, and written informed consent was obtained before the procedure.
All patients received spinal anesthesia under strict aseptic precautions at L3–L4 or L4–L5 interspinous space through a midline approach in sitting position using 25G Quincke's tip spinal needle after free-flow of cerebrospinal fluid without blood staining. Premedication and other medications were similar in both groups. Immediately after the subarachnoid block, each patient was positioned supine. Hemodynamic parameters (heart rate [HR], noninvasive blood pressure, and SpO2) were recorded every 5 min for the first 30 min, after that every 15 min until the end of surgery. The duration of surgery was recorded.
Bilateral sensory block level was evaluated by a blinded assessor with a pinprick test every 2 min in the first half an hour then at every 5 min interval until complete resolution of sensory anesthesia. Any grade of block failure was excluded from the study, and the patients were then converted to general anesthesia.
The pain was assessed using a VAS with a 0–10 scale, with 10 being the worst pain. Postoperative VAS was measured every 30 min until the VAS score was ≥4, or the patient requested rescue analgesia. We used intravenous tramadol 2 mg/kg as rescue analgesia.
All statistical analysis was performed using SPSS 22.0 software package (SPSS Inc., Chicago, IL, USA). T- test for independent samples was used to compare two groups for data with a normal distribution. Yates's continuity correction test (Chi-square test) and Fisher's exact test were used for comparison of qualitative data. All data were summarized as Mean± standard deviation for continuous variables/numbers and as percentages for categorical variables. P < 0.05 was considered statistically significant.
| Results|| |
A total of seventy patients completed the study. Demographic data including age, sex, height, weight, BMI, ASA status, and surgery duration were statistically comparable in both the groups [Table 1].
[Table 2] shows that the time for the two-segment regression of sensory blockade was in favor of Group N (137 ± 6.21 vs. 120.4 ± 6.44 min, P < 0.001). The duration of the sensory block was also significantly longer in Group N (297.4 ± 19.01 vs. 254.45 ± 20.69 min, P < 0.001). The mean duration of analgesia (time to first rescue analgesia) was longer in Group N (318.2 ± 14.14 vs. 152.42 ± 11.96 min).
|Table 2: The sensory blockade, motor blockade, and duration of analgesia|
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[Table 3] shows that all patients had VAS <4 up to 240 min in both groups. There was a statistically significant difference in the number of patients having VAS ≥4 in Group F versus Group N at 270 min and 300 min (P < 0.001). The mean HR [Figure 1], mean arterial pressure [Figure 2], mean SpO2, and mean respiratory rate were statistically comparable in both groups at baseline, intraoperatively, and postoperatively. None of the patients in any group developed respiratory depression or hypoxia. Other adverse effects such as Postoperative nausea vomiting (PONV), pruritus, hypotension, bradycardia, and shivering were comparable in both groups [Table 4].
| Discussion|| |
Subarachnoid block reduces the risk of endocrine-metabolic response to surgery as compared to general anesthesia. Shorter duration of motor block is desirable as it facilitates early ambulation, which helps in the prevention of complications such as pressure ulcer, venous stasis, deep vein thrombosis, urinary incontinence, and provides early recovery. Commonly used LA, such as lignocaine, hyperbaric bupivacaine, and L-bupivacaine, provides excellent subarachnoid block at usual doses but less reliable block if doses are reduced because of early mobilization.
Ropivacaine is useful in terms of producing shorter duration motor block, less CNS and cardiac toxicity, early ambulation, less hospital stay, and good-quality postoperative analgesia with less dose-dependent adverse effects. Ropivacaine blocks C fibers (pain) and Aδ faster and completely than Aα (motor) fibers, which facilitates early ambulation and good postoperative analgesia. Intrathecal opioids as adjuvants bind to G-protein linked pre- and postsynaptic opioid receptors in dorsal horn laminae I and II, which leads to K+ channel opening (μ,δ) and Ca+2 channel closure (k), with an overall reduction in intracellular calcium. This reduces the release of excitatory transmitters (glutamate and substance P) from presynaptic C fibers, but not A fiber terminals with the consequent reduction in nociceptive transmission.
In this study, we compared nalbuphine with fentanyl as an adjuvant to 0.75% isobaric ropivacaine in the subarachnoid block in seventy patients in two groups (n = 35 each) underwent lower limb elective orthopedic surgeries. Baseline parameters, demographic profile, and duration of surgery were statistically comparable in both the groups. The primary outcome measure of our study was the duration of analgesia, and secondary outcome measures were onset and duration of sensory and motor block, two-segment regression time from the highest sensory block, hemodynamic parameters, and observation for adverse effects.
Fentanyl and nalbuphine both provided adequate postoperative analgesia up to 240 min, but after this time point, only nalbuphine provided sustained analgesia. The mean duration of postoperative analgesia was significantly prolonged by nalbuphine (318.2 ± 14.14 min) in comparison to the fentanyl group (275.6 ± 18.76 min) (P < 0.0001). Fentanyl is μ-agonist, and usually have μ-receptor based side effects like emesis, pruritus. Nalbuphine is κ agonist–μ antagonist which attenuates the μ-opioid side effects and enhances the κ-mediated analgesia.
While studying the sensory onset and progress, we found that the cephalad spread of LA was slower (but insignificant, P = 0.07) in the nalbuphine group, and the maximum level of T6 was achieved in 74.29% of patients in comparison to fentanyl (91.43%). Similar levels were found in the studies done by Murali and Narsaiah.
Our results coincide with the study done by Seetharam and Bhat using 0.75% isobaric ropivacaine with fentanyl. Time to achieve peak sensory level was also statistically comparable in the fentanyl and nalbuphine group, similar to other studies.,
The mean time for two-segment regression of sensory block was significantly prolonged by nalbuphine (137 ± 6.21 min) in comparison to fentanyl (120.4 ± 6.44 min) (P < 0.001), similar to the results reported by Gupta et al. Borah et al. used different doses of nalbuphine in 100 patients for elective lower limb surgeries and found that the addition of an increasing dose of nalbuphine as an adjuvant prolongs the two-segment regression time as does in our study too.
The mean duration of sensory block was significantly prolonged by nalbuphine (297.40 ± 19.01 min) in comparison to the fentanyl group (254.45 ± 20.69 min) (P < 0.001), similar to the other study. The mean time for onset of motor block was statistically comparable in fentanyl and nalbuphine. Naaz et al. also found similar results. The mean duration of motor block was significantly prolonged by nalbuphine (189.97 ± 14.92 min) in comparison to the fentanyl group (152.42 ± 11.96 min) (P < 0.001).
PONV and pruritus occurred more with fentanyl than nalbuphine, but the differences were statistically insignificant. The incidence of other adverse effects such as hypotension, bradycardia, shivering, and postoperative sedation was minimal in both the groups and found to be statistically insignificant.
The effect of these drugs on patients with comorbid conditions and extreme age was not studied and will need further research.
| Conclusions|| |
We concluded that nalbuphine significantly prolongs the duration of sensory block, duration of motor block, and duration of postoperative analgesia in comparison to fentanyl, when used as an intrathecal adjuvant to 0.75% isobaric ropivacaine in elective orthopedic lower limb surgeries, with minimal adverse effects.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Shukla D, Verma A, Agarwal A, Pandey HD, Tyagi C. Comparative study of intrathecal dexmedetomidine with intrathecal magnesium sulfate used as adjuvants to bupivacaine. J Anaesthesiol Clin Pharmacol 2011;27:495-9.
] [Full text]
Stocks GM, Hallworth SP, Fernando R, England AJ, Columb MO, Lyons G. Minimum local analgesic dose of intrathecal bupivacaine in labor and the effect of intrathecal fentanyl. Anesthesiology 2001;94:593-8.
Vampugalla PS, Vundi VR, Perumallapalli KS, Kumar CV, Kambar C, Mahalakshmi M, et al
. A comparative study of intrathecal ropivacaine with fentanyl and L-bupivacaine with fentanyl in lower abdominal and lower limb surgeries. Int J Basic Clin Pharmacol 2015;4:1147-55.
Oǧün CO, Kirgiz EN, Duman A, Okesli S, Akyürek C. Comparison of intrathecal isobaric bupivacaine-morphine and ropivacaine-morphine for Caesarean delivery. Br J Anaesth 2003;90:659-64.
American Society of Anesthesiologists Task Force on Neuraxial Opioids, Horlocker TT, Burton AW, Connis RT, Hughes SC, Nickinovich DG, et al
. Practice guidelines for the prevention, detection, and management of respiratory depression associated with neuraxial opioid administration. Anesthesiology 2009;110:218-30.
Prabhakaraiah UN, Narayanappa AB, Gurulingaswamy S, Kempegowda K, Vijaynagar KA, Hanumantharayappa NB, et al
. “Comparison of nalbuphine hydrochloride and fentanyl as an adjuvant to bupivacaine for spinal anesthesia in lower abdominal surgeries:” A randomized, double-blind study. Anesth Essays Res 2017;11:859-63.
] [Full text]
Payen JF, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou JL, et al
. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: A prospective multicenter patient-based study. Anesthesiology 2007;106:687-95.
Sultan MA, Ali Shams TM, Mageed NA, El-ebidy MG. Intrathecal hyperbaric ropivacaine versus hyperbaric bupivacaine in geriatric hypertensive patients. Benha M J 2005;22:479.
Simpson D, Curran MP, Oldfield V, Keating GM. Ropivacaine: A review of its use in regional anaesthesia and acute pain management. Drugs 2005;65:2675-717.
McQuay HJ, Sullivan AF, Smallman K, Dickenson AH. Intrathecal opioids, potency and lipophilicity. Pain 1989;36:111-5.
Murali CH, Narsaiah GL. Effects of fentanyl on isobaric ropivacaine in subarachnoid anaesthesia for lower abdominal and lower extremity surgeries. Int J Res Med Sci 2016;4:2850-5.
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. [Full text]
Gupta K, Singh S, Sharma D, Gupta PK, Krishan A, Pandey MN. Intrathecal fentanyl as an adjuvant to 0.75% isobaric ropivacaine for infraumbilical surgery under subarachnoid block: A prospective study. Saudi J Anaesth 2014;8:64-8.
Babu KV, Kumar GP, Harinath G. Evaluation of the efficacy of intrathecal fentanyl versus intrathecal nalbuphine as an adjuvants to 0.75% ropivacaine for postoperative pain relief in cesarean section: A double-blind randomized comparative study. Int J Sci Study 2017;5:5-10.
Gupta K, Rastogi B, Gupta PK, Singh I, Bansal M, Tyagi V. Intrathecal nalbuphine versus intrathecal fentanyl as an adjuvant to 0.5% hyperbaric bupivacaine for orthopedic surgery of lower limbs under subarachnoid block: A comparative evaluation. Indian J Pain 2016;30:90-5. [Full text]
Borah TJ, Dey S, Yunus M, Dev P, Karim HMR, Bhattacharyya P. Effect of different doses of intrathecal nalbuphine as adjuvant to ropivacaine in elective lower limb surgeries: A dose finding study. Indian J Anaesth 2018;62:865-70.
] [Full text]
Naaz S, Shukla U, Srivastava S, Ozair E, Asghar A. A comparative study of analgesic effect of intrathecal nalbuphine and fentanyl as adjuvant in lower limb orthopaedic surgery. J Clin Diagn Res 2017;11:UC25-8.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]