Introduction: This study aims to evaluate the safety and the efficacy of Nalbuphine with fentanyl as an intrathecal adjuvant to hyperbaric bupivacaine. The objective to study the onset and duration of sensory blockage; time to two segment regression; hemodynamic changes. Materials and Methods: Two groups of thirty ASA Gr I and II patients of either gender were randomly assigned. Group I patients will get 0.8 mg (1 mL) of nalbuphine and 12.5 mg (2.5 mL) of 0.5 percent hyperbaric bupivacaine. Group II patients will receive 12.5 mg and 25 μg of Fentanyl (1 mL). Hemodynamics, sensory and motor block, early postoperative analgesia and side effects were examined. The study included 18–55-year-old male and female patients. The study excluded patients with cardiac arrhythmias, heart blocks, or bradycardia; a known allergy to the test drug; a gross spinal abnormality, localized skin sepsis, haemorrhagic diathesis, neurological involvement/diseases; head injuries or raised intracranial pressure; and hemodynamic instability. Results: Number of rescue analgesia in 24 hrs was significantly less needed among Hyperbaric bupivacaine with nalbuphine group. Systolic blood pressure fluctuation was high among hyperbaric bupivacaine with fentanyl than Hyperbaric bupivacaine with nalbuphine group. Diastolic blood pressure fluctuation was relatively greater among hyperbaric bupivacaine with fentanyl than nalbuphine group. SPO2 saturation fluctuation was almost similar in both the groups. The fluctuation between the groups was not statistically significant. Among hyperbaric bupivacaine with nalbuphine group 4 reported sedation and two reported nauseas. Among hyperbaric bupivacaine with fentanyl group two had chest pain. Conclusion: In this clinical study, nalbuphine added to hyperbaric bupivacaine at 0.5 percent was more efficient than fentanyl at enhancing postoperative analgesia and extending sensory motor blockade without increasing unpleasant effects.

Historically, opioids have been the drug of choice to use in conjunction with spinal anaesthetics as an adjuvant. It would appear that nalbuphine, which acts as both an antagonist for the u receptor and an agonist for the kappa receptor, is an appropriate adjuvant for local anaesthetics. After surgery, people understandably worry a great deal about their level of pain. It has the potential to make patients uncomfortable, interfere with their health and ultimately extend the length of their hospital stay [1]. On the other hand, it may lead to an unfavorable clinical outcome for surgeons. When it comes to postoperative pain management, patients have a wide variety of pharmacological medications and procedures from which to select. In the past few decades, one of the most important aspects of postoperative pain management has been the utilisation of opioids as adjuvants in various regional analgesia approaches [2]. 

Karl August Bier was the first person to employ spinal anaesthesia when he performed the procedure in the year 1898. It is one of the surgical procedures that is used the most frequently, regardless of whether the operation is elective or an emergency in nature [3]. Particularly in situations involving caesarean sections, gynaecological surgery, lower abdominal surgery, orthopaedic surgery and other treatments that are very similar to one another. The spinal block is still the procedure of choice due to its early start, superior blockage, decreased risk of infection, lower failure rates and cost-effectiveness. These benefits outweigh the downsides of a shorter length of block and less postoperative analgesia. Local anaesthetics are renowned for having a relatively limited duration of effect when they are taken on their own [1]. It has been demonstrated that administering doses of different adjuvants intrathecally, such as epinephrine, neostigmine, midazolam, ketamine, fentanyl, buprenorphine, clonidine and dexmedetomidine, can improve the quality and duration of spinal anaesthesia, as well as provide improved postoperative analgesia [4]. Fentanyl has become the most popular opioid in recent years. They have been shown to prolong postoperative analgesia and save sympathetic function when administered intrathecally in conjunction with local anaesthetics. Because it is more lipidsoluble than other opioids, fentanyl is removed from the cerebrospinal fluid more quickly. It offers total intraoperative and postoperative analgesia together with thick blocking without causing any instability to the patient's hemodynamics. It has extremely few adverse effects and those that it does have are easily managed and highly well tolerated by patients [5,6].

This study aims to evaluate the safety and the efficacy of Nalbuphine with fentanyl as an intrathecal adjuvant to hyperbaric bupivacaine. The objective to study the onset and duration of sensory blockage; time to two segment regression; hemodynamic changes.

Sixty patients of either sex belonging to the ASA Gr I and II were randomly allocated into two groups of thirty each. The study period lasts for about 18 months. In group I patient will be receiving 0.8 mg (1 mL) of nalbuphine with 12.5 mg (2.5 mL) of 0.5% hyperbaric bupivacaine and in Group II patient will recieve12.5 mg (2.5 mL) of 0.5% hyperbaric bupivacaine with Fentanyl 25 μg (1 mL). Patients were assessed for hemodynamic changes, sensory and motor block, early postoperative analgesia and adverse effects.

Patients of either gender were considered for inclusion in the study including age of 18 and 55 years. Patients who had cardiac arrhythmias, heart blocks, or bradycardia; patients who had a known allergy to the test drug; patients who had a gross spinal abnormality, localized skin sepsis, haemorrhagic diathesis, neurological involvement/diseases; patients who had head injuries or raised intracranial pressure; and patients who were hemodynamically unstable were excluded from the study.

After obtaining informed consent, 60 patients of either sex will be randomly allocated into two groups of 30 each. Randomization was done by a computer-generated table.

• Group I: Hyperbaric bupivacaine with nalbuphine 

• Group II: Hyperbaric bupivacaine with fentanyl 

The patients were given a preoperative exam the day before their procedure. They were not allowed to eat or drink anything after 10:00 p.m. the previous evening and they were given a tablet of ranitidine 150 mg and a tablet of alprazolam 0.5 mg to take orally as premedication the night before the surgery, along with a small sip of water. The surgery was performed the following morning. After establishing intravenous (IV) access with an 18G cannula, patients will have a preload of 5 ml/kg of Ringer lactate solution administered to them. Monitoring of the patient's heart rate, blood pressure, electrocardiography and oxygen saturation (SpO2) occurred once they were moved into the operating room.

After placing the patient in the left lateral position and taking all necessary aseptic precautions, a spinal block was performed at the lumbar third and fourth interspace through a midline approach and then the patient was positioned in the supine position. The spinal needle used in the procedure was a 25-guage Quincke. Patients in Group ll were given 3 milliliters of hyperbaric bupivacaine at a concentration of 0.5 percent, along with 25 micrograms of fentanyl. Patients in Group I were given 3 millilitres of hyperbaric bupivacaine at a concentration of 0.5 percent, along with 300 micrograms of nalbuphine. Using pure water, the total volume was brought up to 3.5 milliliters. When calculating the time of intrathecal injection, start with 0 seconds. 

The following parameters—heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were recorded during the examination: During the first ten minutes of the operation, the SpO2 and respiratory rate were recorded every two minutes. After that, they were monitored every ten minutes for the remainder of the intraoperative period and at the conclusion of the operation. The time of onset of sensory blockade, the height of sensory blockade, motor blockade according to the Bromage scale, total duration of sensory blockade and motor blockade, quality of analgesia (visual analogue score), two-segment sensory regression time, time to first rescue analgesic and number of rescue analgesics in 24 hours were also monitored. These parameters were recorded and analysed. The measurements of the vital signs were taken at time 0, after 5 minutes, then every 10 minutes for the first hour and then every half hour until the end of the operation.

In a study conducted by Thote et al., the size of the sample was determined using the outcome variable “length of grade 4 motor block”. Total sample size estimated is 60. 30 per group. 

For continuous variables, descriptive statistics were supplied as the mean together with the standard deviation and for categorical variables, frequencies along with percentages were given. Chi-Square was employed with a level of significance of 5% to determine whether or not there was statistical significance. When the anticipated cell count is lower than 5, the Fischer exact test is positive. IBM SPSS Statistics for Windows, Version 26.0, developed by IBM Corp. and based in Chicago, Illinois, was used to do statistical analysis on the collected data.

The mean age of the study participants was comparable between the groups. The mean age was 41.67±10.20 years among bupivacaine with nalbuphine group and 42.37±10.22 years among bupivacaine with fentanyl group. The mean weight of the study participants was comparable between the groups. The mean weight was 58.53±6.78kg among hyperbaric bupivacaine with nalbuphine Group and 58.60±6.11kg among Hyperbaric bupivacaine with fentanyl group. The mean duration of surgery of the study participants was comparable between the groups. 

Table 1: Distribution of Study Variable Among the Study Participants (N = 60)

Table 2: Distribution of Number of Rescue Analgesia In 24 HR the Study Participants (N = 60)

Figure 1: Distribution Of Systolic Blood Pressure Among the Study Participants (N = 60) 

Figure 2: Distribution of Diastolic Blood Pressure Among the Study Participants (N = 60)

The mean duration was 67.63±17.42 among Hyperbaric bupivacaine with nalbuphine group and 67.50±13.79 among Hyperbaric bupivacaine with fentanyl group. Onset of analgesia was statistically high among Hyperbaric bupivacaine with fentanyl group. Hyperbaric bupivacaine with nalbuphine group had mean onset time of 114.07±15.83 and hyperbaric bupivacaine with fentanyl group had 176.13±7.21 (Table 1).

Figure 3: Distribution of SPO2 Among the Study Participants (N = 60) 

Figure 4: Distribution of Side Effects Among the Study Participants (N = 60) 

Spread of analgesia was statistically less among Hyperbaric bupivacaine with fentanyl group. Hyperbaric bupivacaine with nalbuphine group had mean spread of analgesia time of 6.37±0.76 and hyperbaric bupivacaine with fentanyl group had 5.87±1.16. 

Onset of motor block was statistically high among hyperbaric bupivacaine with fentanyl group. Hyperbaric bupivacaine with nalbuphine group had onset of motor block time of 101.83±33.25 and hyperbaric bupivacaine with fentanyl group had 166.63±8.18. Duration of analgesia was statistically less among hyperbaric bupivacaine with fentanyl group.

Total duration of motor block was statistically less among Hyperbaric bupivacaine with fentanyl group. Hyperbaric bupivacaine with nalbuphine group had total duration of motor block time of 3.41±0.21 and hyperbaric bupivacaine with fentanyl group had 3.13±0.31. Total mean VAS score was statistically less among Hyperbaric bupivacaine with nalbuphine group. Total mean time of first rescue analgesia was statistically less among Hyperbaric bupivacaine with nalbuphine group. Total mean time of first rescue analgesia was statistically less among Hyperbaric bupivacaine with nalbuphine group. 

Number of rescue analgesia in 24 hrs was significantly less needed among Hyperbaric bupivacaine with nalbuphine group (Table 2).

Diastolic blood pressure fluctuation was relatively greater among hyperbaric bupivacaine with fentanyl than nalbuphine group. It was found to be statistically significant (Figure 2).

SPO2 saturation fluctuation was almost similar in both the groups. The fluctuation between the groups was not statistically significant (Figure 3). 

Among hyperbaric bupivacaine with nalbuphine group 4 reported sedation and two reported nauseas. Among hyperbaric bupivacaine with fentanyl group two had chest pain (Figure 4). 

In our study the mean age of the study participants was comparable between the groups. The mean age was 41.67±10.20 years among bupivacaine with nalbuphine group and 42.37±10.22 years among bupivacaine with fentanyl group. In Prabhakaraiah et al. [7], the mean age was 42.57±0.45 years among bupivacaine with nalbuphine group and 42.93±12.06 years among bupivacaine with fentanyl group. In Sharma et al. [8], the mean age was 34.95±14.88 years among nalbuphine group and 29.32±11.43 years among fentanyl group. Our study age was comparable with other studies.

In our study the mean weight of the study participants was comparable between the groups. The mean weight was 58.53±6.78kg among hyperbaric bupivacaine with nalbuphine Group and 58.60±6.11kg among Hyperbaric bupivacaine with fentanyl group. In Prabhakaraiah et al. [7], the mean BMI was 24.70±3.20 kg/m² among bupivacaine with nalbuphine group and 23.58±3.05 kg/m² among bupivacaine with fentanyl group. In Sharma et al8 the mean age was 63.64±5.45 kg among nalbuphine group and 65.36±6.11kg among fentanyl group. Our study weight of the study participants was comparable with other studies.

 In our study the mean duration of surgery of the study participants was comparable between the groups. The mean duration was 67.63±17.42 among Hyperbaric bupivacaine with nalbuphine group and 67.50±13.79 among Hyperbaric bupivacaine with fentanyl group. In Prabhakaraiah et al. [7], the mean duration of surgery was 63.83±18.60min among bupivacaine with nalbuphine group and 61.67±16.37min among bupivacaine with fentanyl group. In Sharma et al. [3,5], the mean duration of surgery was 98.86±11.95 among nalbuphine group and 99.36±6.11 among fentanyl group. Our study duration of surgery of the study participants was comparable with other studies.

 In our study pulse rate fluctuation was high among hyperbaric bupivacaine with fentanyl group than hyperbaric bupivacaine with nalbuphine. It was found to be statistically significant. 

Systolic blood pressure fluctuation was high among hyperbaric bupivacaine with fentanyl than 

Hyperbaric bupivacaine with nalbuphine group. It was found to be statistically significant. Diastolic blood pressure fluctuation was relatively greater among hyperbaric bupivacaine with fentanyl than nalbuphine group. It was found to be statistically significant. SPO2 saturation fluctuation was almost similar in both the groups. The fluctuation between the groups was not statistically significant. In Prabhakaraiah et al. [7], the mean heart rate was 87.03±15.75/min among bupivacaine with nalbuphine group and 85.90±13.16/min among bupivacaine with fentanyl group. In Prabhakaraiah et al. [8], the mean systolic blood pressure was 133.17±12.72mm of Hg among bupivacaine with nalbuphine group and 133.17±14.64mm of Hg among bupivacaine with fentanyl group. In Prabhakaraiah et al. [7], the mean diastolic blood pressure was 99.90±7.98mm of Hg among bupivacaine with nalbuphine group and 102.43±9.83mm of Hg among bupivacaine with fentanyl group. 

 In our study onset of analgesia was statistically high among Hyperbaric bupivacaine with fentanyl group. Hyperbaric bupivacaine with nalbuphine group had mean onset time of 114.07±15.83 and hyperbaric bupivacaine with fentanyl group had 176.13±7.21. In Gupta et al. [9] the duration of sensory block and motor block was significantly enhanced by the addition of intrathecal nalbuphine as compared to intrathecal fentanyl in the present study. The results of the present study correlates well with other studies where it was observed that addition of nalbuphine allowed a significant reduction in pain score. 

 Mukherjee et al. conducted research on the duration of analgesia using varying dosages of intrathecal nalbuphine, with the goal of determining the optimal dose of intrathecal nalbuphine that could prolong the postoperative analgesia without increasing the number of adverse effects. Their research came to the conclusion that increasing the doses of nalbuphine used as an adjuvant to hyperbaric bupivacaine at a concentration of 0.5 percent did not result in any adverse effects, but did increase the amount of pain relief achieved [10]. 

 Yoon et al. conducted a study on sixty obstetric patients who were scheduled to have spinal anaesthesia prior to having a caesarean section. Patients were given morphine 0.1 mg, nalbuphine 1 mg, or morphine 0.1 mg with nalbuphine 1 mg in addition to 0.5 percent bupivacaine (10 mg). After the study, researchers came to the conclusion that effective analgesia was prolonged in the morphine group and the morphine with nalbuphine group; however, the incidence of pruritus was significantly lower in the nalbuphine group [11]. The findings of their investigation are consistent with the ones we got from our own. 

 After transurethral excision of the bladder tumour, Mostafa et al. examined the analgesic efficacy, duration of analgesia and side effects of intrathecal tramadol 50 mg against nalbuphine 2 mg for postoperative analgesia. Both medications were administered by the intrathecal route. They observed that the strength and duration of motor block and sensory analgesia were not significantly different from one another clinically. The patients experienced a low risk of experiencing side effects such as hypotension, bradycardia, itching, respiratory depression, nausea and other symptoms and they were able to handle these effects well. The sedation score was also the same for both groups, however the nalbuphine group required fewer doses of rescue analgesia than the other group [12]. In the current study, we compared the effects of fentanyl and nalbuphine on the length of motor and sensory block and we discovered that there was a statistically significant difference between the two. During the procedure, there were no incidents of anxiety or discomfort among any of the patients and there were no adverse medication reactions [13]. 

In randomized control research on older patients, Sapate et al. looked at the effects of intrathecal nalbuphine (0.5 mg) combined with spinal bupivacaine (0.5 percent) in a volume of 3 milliliters. The procedures involved the lower abdominal region. They came to the conclusion that nalbuphine offered a higher quality of SAB as compared to bupivacaine on its own and it also improved the postoperative analgesia. In their study, none of the participants experienced any adverse effects [14]. 

In spinal anaesthesia for lower limb orthopaedic surgery, Verma et al. evaluated the postoperative analgesic efficacy of intrathecal tramadol (50 mg) with nalbuphine (2 mg) as an adjuvant to hyperbaric bupivacaine (12.5 mg). They came to the conclusion that adding nalbuphine to hyperbaric bupivacaine improved postoperative analgesia and prolonged the duration of sensorimotor block, both of which occurred after lower limb orthopaedic surgery. When compared to the use of bupivacaine alone, intrathecal tramadol was unable to produce a discernible improvement in the postoperative analgesia experienced by the patients [15]. The findings of their research are consistent with the findings of our study, which is quite encouraging. 

In a randomised control study, Ahmed et al. examined the potentiating effect of intrathecal nalbuphine with bupivacaine for postoperative analgesia. The researchers used these three doses to compare the potentiating effect of intrathecal nalbuphine with bupivacaine. They came to the conclusion that intrathecal bupivacaine combined with nalbuphine greatly prolonged postoperative analgesia in comparison to the group that served as the control and that a dose of 1.6 mg exhibited the best results [16].

In this clinical research, the addition of nalbuphine as an adjuvant to hyperbaric bupivacaine at a concentration of 0.5 percent was shown to be more effective than fentanyl at enhancing postoperative analgesia and extending the duration of sensory motor blockade, with no appreciable increase in adverse effects. 

Authors Contribution

• Conceptualization, Data collection, Manuscript drafting and critical revision of the manuscript – Dr Satish Patel

•  Manuscript drafting and data collection: Dr. Virendra Rastogi

• Manuscript revision and supervision: Dr. Pushkar Ranjan

• Statistical Analysis and data curation: Dr. Pushkar Ranjan

• Supervision and Critical revision of Manuscript: Dr. Emmanuel kuruvilla

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