|Year : 2020 | Volume
| Issue : 4 | Page : 203-208
Comparative analysis of intrathecal nalbuphine vs fentanyl as an adjuvant to bupivacaine for urological procedures
Kamakshi Garg1, Pallavi Garg2, Sunil Katyal1
1 Department of Anesthesiology, Dayanand Medical College & Hospital, Civil Lines, Tagore Nagar, Ludhiana, Punjab, India
2 Civil Hospital, Barnala, Punjab, India
|Date of Submission||07-Jul-2020|
|Date of Decision||09-Sep-2020|
|Date of Acceptance||09-Sep-2020|
|Date of Web Publication||09-Dec-2020|
Dr. Kamakshi Garg
Department of Anesthesiology, Dayanand Medical College, Civil Lines, Tagore Nagar, Ludhiana 141001, Punjab.
Source of Support: None, Conflict of Interest: None
Background: Opioids have been used as additives to bupivacaine in spinal block to enhance their action and analgesia. The aim of the study was to assess the effectiveness of adding intrathecal nalbuphine or fentanyl as an adjuvant to bupivacaine in spinal anesthesia for patients undergoing the transurethral resection of the prostate (TURP). This is a single-center, prospective, double-blind, randomized study. Materials and Methods: Sixty men (40–80 years) undergoing TURP received an intrathecal injection with 2.5 mL of 0.5% hyperbaric bupivacaine with fentanyl 25 µg (Group 1) or nalbuphine hydrochloride 0.8 mg (Group 2) in this prospective, randomized, double-blind study. The onset and duration of sensory and motor block, hemodynamic parameters, and incidence of adverse effects were compared between the groups. Results: Patients in the nalbuphine group reported significantly prolonged sensory block (198.60 ± 16.8min) compared to patients in the fentanyl group (185.40 ± 22.2min), (P < 0.001). Similarly, patients in the nalbuphine group had a longer motor block (210.60 ± 19.8min) in comparison to those in the fentanyl group (194.40 ± 21min; P < 0.001). Intraoperative hemodynamic variability was comparable in both the groups. Postoperative pain was significantly higher in the fentanyl group (80%) as compared to the nalbuphine group (13.3%) (P < 0.001). Conclusion: Intrathecal nalbuphine is a safe and valuable alternative to intrathecal fentanyl for spinal anesthesia.
Keywords: Adjuvant, fentanyl, nalbuphine, spinal anesthesia, transurethral resection of the prostate
|How to cite this article:|
Garg K, Garg P, Katyal S. Comparative analysis of intrathecal nalbuphine vs fentanyl as an adjuvant to bupivacaine for urological procedures. MGM J Med Sci 2020;7:203-8
|How to cite this URL:|
Garg K, Garg P, Katyal S. Comparative analysis of intrathecal nalbuphine vs fentanyl as an adjuvant to bupivacaine for urological procedures. MGM J Med Sci [serial online] 2020 [cited 2021 Mar 4];7:203-8. Available from: http://www.mgmjms.com/text.asp?2020/7/4/203/302808
| Introduction|| |
Spinal anesthesia is the most commonly used technique for prostatic surgeries and bupivacaine is the most commonly used intrathecal local anesthetic agent. However, postoperative pain control is a major problem while using only local anesthetics as they are associated with a relatively short duration of action, and thus early rescue analgesic intervention is needed in many cases during the postoperative period. To avoid this, various additives have been used along with bupivacaine to increase their duration of action and efficacy. They increase the speed of the onset of neural block, improve the quality, and prolong the duration of the block. Fentanyl is a lipophilic opioid with a rapid onset following intrathecal injection, without causing respiratory depression as it does not migrate to the 4th ventricle. Studies have demonstrated that it improves the duration of sensory anesthesia and postoperative analgesia without producing significant side effects. Nalbuphine is an agonist–antagonist opioid that is structurally related to oxymorphone and naloxone. It has the potential to attenuate the μ-opioid effects and enhance the ĸ-opioid receptor-mediated effects. It has been recently used intrathecally for cesarean sections, infra-umbilical surgeries, lower limb orthopedic surgeries, and for the prevention of intrathecal morphine-induced pruritis. Very few studies have compared the effects of adding intrathecal nalbuphine (opioid agonist–antagonist) or fentanyl (opioid agonist) as an adjuvant to bupivacaine. In this perspective, randomized, double-blind study, we tried to compare fentanyl and nalbuphine as adjuvants to bupivacaine in a subarachnoid block in terms of onset and duration of sensory and motor block as the primary outcome and intraoperative and postoperative hemodynamic profile as a secondary outcome.
| Materials and methods|| |
The present study is a randomized clinical trial conducted in the Department of Anaesthesiology, at a tertiary care hospital from January 2016 to July 2017 after approval by the Institutional Ethics Committee. The study conformed to the ethical guidelines of the 2013 Helsinki declaration. This study is registered in the Clinical Trial Registry of India (CTRI/2019/09/021013). A total of 60 patients, aged 40 to 80 years and American Society of Anaesthesiologists (ASA) physical status I and II, scheduled to undergo transurethral resection of the prostate (TURP) was included in the study.
We excluded patients who refused consent for the subarachnoid block had a history of anaphylaxis to local anesthetics and allergic to the drugs to be used, on anticoagulant medication or severe bleeding disorders, history of pre-existing neurological disease, infection at the site of injection, history of cardiac or respiratory failure or those with spinal deformities. Failure of spinal anesthesia, inadequate block, or conversion into general anesthesia was also excluded. Patients eligible for participation in the study was allocated into two groups and randomized by computer-generated random numbers. Group I received an intrathecal injection of 2.5 mL of 0.5% hyperbaric bupivacaine + 0.5 mL fentanyl (25 µg) and Group II received an intrathecal injection of 2.5 mL of 0.5% hyperbaric bupivacaine + 0.5 mL nalbuphine hydrochloride (0.8 mg).
A thorough pre-anesthetic checkup was conducted 1 day before surgery and patients were kept fasting 6h before surgery. Tab alprazolam (0.25 mg) and tab ranitidine (150 mg) were given orally to all patients’ night before surgery and in the morning of surgery. On the day of surgery, the drug codes in a sealed envelope numbered 1 to 60 were opened by the designated consultant of the work area just before the administration of anesthesia. An anesthesiologist not involved in the study prepared 3 mL of study drug in a 5 mL syringe. The drug was then handed over to the attending anesthesiologist in a coded form who was blind to the nature of the drug given to him/her. Subarachnoid block was performed under all aseptic precautions, and patients were given 3 mL of the study drug using a 26G Quincke’s spinal needle in the sitting position. The patient is then repositioned supine.
The beginning, time duration, the highest level of sensory block, and the time to reach the highest dermatomal level of sensory block were noted. Similarly, motor block onset, time to complete motor block recovery, and duration of spinal anesthesia or time to first rescue analgesic request were recorded. The time period between subarachnoid block placement and disappearance of pain at T8 dermatome, as seen by the pinprick method, was taken as the onset of sensory block. The highest level of sensory block was evaluated by pinprick at the midclavicular line anteriorly every 5min for the first 15min and then every 15min till 90min. The duration of the sensory block was defined as the time to regression to two segments in the maximum block height, evaluated by a pinprick. The onset of motor block was assessed by the modified Bromage score. Secondary outcomes were to compare post-operative analgesia and side effect profile of the two drugs.
Intraoperatively, the level of sensory block was recorded 0, 5, 10, and 15min after intrathecal injection, and subsequently every 15min. Motor block was recorded till the modified Bromage score was 3. Hemodynamic parameters were continuously monitored and were recorded 0, 5, 10, and 15min after intrathecal injection, and subsequently every 15min till the end of surgery. Atropine 0.6 mg intravenously was given when the heart rate decreased below 50 beats per minute. Intermittent doses of ephedrine 3 mg intravenously were given when the blood pressure decreased by more than 20% below the pre-anesthetic level. Side effects like nausea, vomiting, pruritus, hypotension, bradycardia, respiratory depression were also recorded for the first 6h following intrathecal injection. At the completion of surgery, all hemodynamic parameters, sensory, and motor block were recorded, and then the patient was shifted to the recovery room.
In the immediate postoperative period, hemodynamic parameters were recorded every 15min for the first 60min and then hourly till the fourth hour and then 4 hourly till stay in the recovery room or completion of 24 hours (whichever was first). Duration of sensory blockade was noted by assessing the level of the sensory block after every 15min until the time of two-segment regression or regression to T10 level. Motor block recovery was assessed every 15min till the complete return of motor function of the lower extremity (modified Bromage score 0). All observations were recorded by an anesthesiologist who was blinded to the group allocation of the patient.
Quality of postoperative analgesia was assessed using the Visual Analogue Scale (VAS) which ranges from 0 indicating no pain to 10 indicating intractable pain with varying levels of intensity in between, every 15min till the first request of analgesia. Any patient presenting with VAS more than or equal to four were given an injection Tramadol 50 mg intravenously slowly. Patients were shifted from recovery room when the motor block was completely resolved.
Sample size calculation
A post hoc power analysis was conducted using the software package, G*Power (Faul and Erdfelder 1992). The alpha level used for this analysis was P < 0.05 and beta was 0.20. The sample size was estimated from the results of a previous study using the duration of the motor block as the parameter, which is the primary outcome of our study. Our sample size came out to be 30 subjects per group at the power of 0.99 and with an effect size of 1.69 with a 10% chance of error with α = 0.05, β = 0.20, and a confidence interval of 95%.
Data were analyzed in SPSS (Statistical Package for the Social Science) SPSS 21 version statistical program for Microsoft Windows. Data were described in terms of mean ± standard deviation and frequencies and percentages. Based on the distribution and scales of measurement, appropriate tests like t-test, Maan–Whiney U test, χ2, or Fisher’s exact tests were utilized to compare variables between the study groups. A probability value (P-value) less than 0.05 was considered statistically significant.
| Results|| |
We divided 60 patients in our study into two groups of 30 each. Demographic data in terms of age, gender, weight, and height were similar in both groups. There was no significant difference in the duration of surgery also among the two groups [Table 1].
The mean time of onset of sensory and motor block in the fentanyl and nalbuphine group was statistically insignificant. However, the duration of the sensory block was significantly higher in the nalbuphine group (198.60 ± 16.8min) as compared to the fentanyl group (185.40 ± 22.2min), (P < 0.001). Similarly, the mean duration of motor block was significantly prolonged among patients of the nalbuphine group (210.60 ± 19.8min) as compared to those in the fentanyl group (194.40 ± 21min), (P < 0.001). [Table 2]. The highest level of sensory block was T8 in both the study groups and the meantime to reach the maximum sensory level was insignificant in both the groups. The mean duration of sensory and motor block was significantly higher in the nalbuphine group as compared to the fentanyl group (P < 0.001).
|Table 2: Comparing various block characteristics among the two treatment groups|
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Intraoperatively, heart rate, systolic and diastolic blood pressure, respiratory rate, and oxygen saturation were statistically similar among patients in both the study groups. MAP never decreased to less than 20% of baseline values in both the groups [Figure 1]. In the postoperative period, all the hemodynamic parameters were statistically similar in both the study groups [Figure 2]. Incidence of pruritis (43.33%) and shivering (13.3%) was statistically significant in the fentanyl group during the first 30min and none of the patients in the nalbuphine group had pruritis and shivering (P < 0.05) [Figure 3]. Postoperative pain (VAS>4) was significantly higher in the fentanyl group as compared to the nalbuphine group (p-value <0.001). We also observed a significantly prolonged mean time of first rescue analgesic request in the nalbuphine group (330 ± 34.80min) as compared to that in the fentanyl group (204 ± 57min) p-value <0.01.
| Discussion|| |
Spinal anesthesia is commonly used in urological surgeries, especially in those with cardiac and respiratory problems. TURP surgery usually lasts less than 60min, and early recovery and discharge are expected. Conventional spinal anesthesia has complications such as hemodynamic variations, urinary retention, postural headache, and transient neurological symptoms, which may occur due to the local anesthetic agent sympatholytic effect. We evaluated the effects of the addition of opioid (fentanyl) versus non-opioid (nalbuphine) as adjuvants to 0.5% hyperbaric bupivacaine in patients undergoing TURP surgery. We chose 0.8 mg dose for nalbuphine, as it is an ideal dose to achieve adequate block characteristics. We observed that the onset of sensory and motor block was comparable between the two study groups. Similar conclusions were drawn by Thote et al., who found the onset of sensory and motor block with 25 µg of fentanyl and 0.5 mg of nalbuphine to be comparable. However, Vashishth et al. noticed that fentanyl is better than nalbuphine in terms of onset of the block in lower abdomen and limb surgeries. Similarly in cesarean patients, Gomaa et al. demonstrated the faster onset of motor block in the fentanyl group when compared to the nalbuphine group, which contradicted our study results.
We found the mean duration of sensory and motor block to be significantly prolonged in the nalbuphine group. Gupta et al. compared 2 mg nalbuphine with 25 μg fentanyl intrathecally as an adjuvant to 17.5 mg hyperbaric bupivacaine in spinal anesthesia for lower limb orthopedic surgery. They noticed a prolonged duration of both sensory and motor blockade in patients who received nalbuphine than in those who received fentanyl. This is in contrast to that observed by Bindra and colleagues, who compared the effect of intrathecal nalbuphine and fentanyl as adjuvants to bupivacaine in cesarean section. They observed that 20 µg fentanyl had a significantly prolonged sensory block as compared to 0.8 mg nalbuphine. Intraoperatively, we observed no difference in the hemodynamic parameters between the two study groups. Similar findings were observed by Tiwari et al., who observed that hemodynamic and respiratory complications were absent, except two patients in the nalbuphine group (400 µg) and one patient in the other nalbuphine group (200 µg) developed bradycardia.
Shivering among two patients in each of the groups was also observed. In our study population, there was only one patient receiving fentanyl who had nausea or vomiting. In the first 30min, 43% and 13% of the patients receiving fentanyl had pruritus and shivering respectively. None of the patients receiving nalbuphine had any of these side effects. Nalbuphine is an opioid agonist–antagonist and its analgesic and possible antipruritic effects mediated via μ- and κ-receptors may explain our findings. Moustafa and Saleh have reported that the addition of 1 mg nalbuphine to 0.2 mg morphine during subarachnoid block antagonizes the morphine-induced adverse effects such as nausea-vomiting and pruritus without any effect on the duration, quality of postoperative analgesia or the degree of postoperative rescue analgesic dose requirement.
Postoperative pain (VAS ≥ 4) was observed in 80% of those receiving fentanyl as compared to 13.3% of those receiving nalbuphine. Also, patients who received intrathecal nalbuphine had a longer duration of postoperative analgesia by approximately 127min as compared to the fentanyl group. Similar to our findings, Bindra et al. found the mean VAS score for postoperative pain to be lower in the nalbuphine group and required a significantly lesser number of rescue analgesics as compared to the fentanyl group.
| Conclusion|| |
In our study population, 0.8 mg nalbuphine resulted in a significant prolongation of the duration of sensory and motor blockade among patients undergoing TURP. They also had a stable intra- and postoperative hemodynamic profile. In addition, patients in the nalbuphine group did not experience nausea/vomiting, pruritus, or shivering. Therefore, intrathecal nalbuphine is a safe and valuable alternative to intrathecal fentanyl for spinal anesthesia in patients undergoing urological procedures.
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Conflict of interest
There are no conflicts of interest
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]