European Journal of Cardiovascular Medicine

Subarachnoid block (SAB) is the preferred mode of anaesthesia for infraumbilical surgeries, unless contraindicated, owing to its numerous benefits over general anaesthesia. It is cost-effective, easy to administer and provides rapid onset of action with lower incidence of side effects, thereby enhancing patient’s comfort [1]

Hyperbaric bupivacaine 0.5% has been a widely used long-acting local anaesthetic in subarachnoid blocks for lower abdominal surgeries for many years. It is known for its increased risk of toxicity with higher concentrations or accidental vascular administration. Consequently, newer alternatives such as ropivacaine and levobupivacaine, which offer similar advantages to bupivacaine but with a lower toxicity profile, have been adopted [2]

Hyperbaric ropivacaine, a long-acting local anaesthetic structurally akin to bupivacaine, exhibits sensory and motor blockade properties similar to its predecessor [2]. It offers improved sensory-motor differentiation and a shorter duration of motor blockade due to its reduced lipophilicity. This feature of ropivacaine is particularly advantageous when a shorter duration of motor blockade is preferred. Additionally, its lower lipophilicity contributes to reduced risks of cardiotoxicity and neurotoxicity [3]

A drawback of using hyperbaric ropivacaine alone is its relatively short duration of action, necessitating early analgesic intervention in the postoperative period. Hence neuraxial adjuvants are employed to enhance or prolong analgesia and to mitigate the adverse effects associated with using either typical or high doses of a single local anaesthetic agent alone [1].Various adjuvants such as fentanyl, morphine, tramadol, dexmedetomidine, clonidine, dexamethasone, neostigmine, ketamine, midazolam etc are incorporated with local anaesthetics to synergistically enhance the quality of anaesthesia [4]

Dexmedetomidine is a highly selective alpha-2 agonist with hypnotic, sedative, anxiolytic, sympatholytic, opioid-sparing and analgesic properties without causing significant respiratory depression [1]. It has unique sedative response of easy transition from sleep to wakefulness allowing the patient to be cooperative and communicative when stimulated [5]

Nalbuphine, a mixed kappa agonist and mu antagonist is a derivative of 14-hydroxymorphine with strong analgesic effect. It has effects of sedation and analgesia with cardiovascular stability due to its affinity to kappa opioid receptors which also causes less incidence of pruritus, nausea, vomiting and minimal respiratory depression [6]

Fewer studies are available comparing intrathecal dexmedetomidine versus nalbuphine as adjuvants to hyperbaric ropivacaine in infraumbilical surgeries. This study compares the efficacy of dexmedetomidine versus nalbuphine with ropivacaine in enhancing the anaesthetic analgesic properties of SAB.

Objectives:

Primary objectives of the study are to compare the time of onset and the duration of sensory and motor block between the groups receiving intrathecal dexmedetomidine and nalbuphine with hyperbaric ropivacaine. Also, the duration of postoperative analgesia is compared between the groups. Secondary objectives include comparison of hemodynamic variability between the two groups and the incidence of any intraoperative or postoperative side-effects and complications.

The prospective, randomised and double blinded study was carried out at Major operation theatre at Hassan Institute of Medical Sciences teaching hospital, Hassan on 80 patients aged 18-60years, weighing around 50-70kg/ height of 155-174cm, belonging to ASA I and II physical status and posted for elective infraumbilical surgeries under SAB. Patients with history of allergy to local anaesthetics/opioids and those who were on medications like beta blockers/ opioids were excluded from the study after obtaining approval from the institutional ethical committee. Informed written consent was taken from the patients.

Patients were randomly allocated into Group RD and Group RN using computer generated sequence. Group RD recieved 3.2ml of 0.75% hyperbaric ropivacaine along with 10 μg of Inj. Dexmedetomidine (0.1ml of dexmedetomidine reconstituted with 0.2ml normal saline) while Group RN received recieved 1mg of inj. Nalbuphine (0.1 ml of nalbuphine reconstituted with 0.2ml normal saline) along with 3.2ml of 0.75% hyperbaric ropivacaine. The total volume of study drug was kept constant in all 80 patients (3.5 ml). The drug was prepared by one anaesthesiologist and was handed over to the other anaesthesiologist in the coded form who performed the study. So, the anaesthesiologist as well as the patient enrolled into the study was blinded about the nature of the study drug.

Prior to performing the lumbar puncture, standard monitoring including electrocardiography, pulse oximetry and non-invasive blood pressure measurement were done and the patient was co-loaded with ringer lactate. Lumbar puncture was done using 25-gauge Quincke spinal needle via median approach in L3-L4 intervertebral space with patients in sitting position under full aseptic precautions. Successful placement of spinal needle in subarachnoid space was confirmed by aspiration of cerebrospinal fluid and the study drug was injected. The patient was placed supine after injecting the drug.

The time of the intrathecal injection was recorded, and clinical parameters, Visual Analog Scale (VAS) scores, and any side effects were monitored. The onset of sensory block was assessed bilaterally along the midclavicular line by evaluating changes in pinprick sensation using a hypodermic needle, continuing until no sensation was detected at the T10 dermatome level. Sensory response was graded as follows: grade 0 for normal sensation, grade 1 for blunted sensation, and grade 2 for no sensation. The highest dermatome level of the sensory block and the time to reach this level were documented. The time for two-segment regression was noted as the highest segment level of sensory block regressed by two spinal cord segments.

The onset of motor block was assessed until complete motor block (grade 3) was achieved, according to the Bromage scale for the limbs: grade 0 for no motor block, grade 1 for inability to raise extended legs, grade 2 for inability to flex knees, and grade 3 for inability to flex ankle joints, with grade 3 indicating complete motor block. The duration of motor block was determined by the time taken for the Bromage motor block to regress from the maximum level (grade 3) to grade 0.

The duration of analgesia was defined as the time from the intrathecal injection to when the VAS score exceeded 3 or when the patient first requested IM/IV analgesia (rescue analgesia). Pain was assessed using a standard 10-point Visual Analog Scale (VAS), where 0 represents no pain and 10 represents the worst possible pain. The VAS Numeric Pain Distress Scale was recorded both before the procedure and postoperatively until the patient requested IM/IV analgesia. Sedation levels were assessed using the Ramsay Sedation Scale.

Intra-operative non-invasive monitoring of vital signs (HR, SBP, DBP, MAP, and SpO2) was performed every 2 minutes for the first 10 minutes, every 5 minutes for the next 20 minutes, every 15 minutes for the following 90 minutes, and every 30 minutes thereafter until the completion of the surgical procedure. Postoperative non-invasive monitoring of vital signs (HR, SBP, DBP, MAP, and SpO2) was conducted once every hour. Oxygen was administered via a face mask at a rate of 4–5 L/min if SpO2 dropped below 90% at any point. Side effects, including hypotension, bradycardia, nausea, vomiting, pruritus, drowsiness, respiratory depression, and urinary retention were monitored, documented, and treated as necessary.

Statistical Analysis:

Data were entered into a Microsoft Excel spreadsheet, and statistical analysis was performed using SPSS software. Categorical data were expressed as percentages and proportions, with the Chi-square test used to assess statistical significance. Continuous data were presented as mean ± standard deviation, and the unpaired t-test was used to determine the mean difference between the two groups. All observations were subjected to statistical evaluation and a p-value of <0.05 was considered statistically significant.

A total of eighty patients were recruited for the study according to the criteria outlined above and were randomly assigned to either group RD or group RN. The demographic characteristics of both groups were similar, as shown in Figure 1.

The onset of sensory and motor blockade was faster in group RD compared to group RN, as demonstrated in Figures 2 and 3, respectively (P<0.05).

The addition of dexmedetomidine to hyperbaric ropivacaine resulted in a significantly longer duration of sensory and motor blockade compared to nalbuphine (P<0.05). Fig. 4 &  

In group RD, the highest level of sensory block was T4 in 5 (12.5%) patients and T6 in 35 (87.5%) patients, whereas in group RN, the highest level reached T4 in 4 (10%) patients and T6 in 36 (90%) patients. No statistically significant differences were observed between the two groups in terms of the highest level of sensory block. Fig 6.

Total duration of analgesia was found to be longer in group RD (660.825 min) than that of group RN (567.5 min) (P>0.005)

Moreover, hemodynamic variables remained consistent without any significant fluctuations, and no adverse events or side effects were recorded in either group throughout the entire study period.

Spinal anaesthesia is a frequently utilized central neuraxial blockade, typically administered for surgeries involving the lower abdomen, pelvis, and lower limbs. It offers several potential advantages, such as eliminating the need for airway instrumentation, providing profound analgesia, maintaining stable hemodynamic, reducing surgical blood loss, and enhancing operating conditions. However, its reported disadvantages include intra-operative anxiety, coughing, hiccups, and unintended patient movement, which can complicate the procedure. In contrast, general anaesthesia keeps the patient immobile and guarantees a secure airway during the procedure. Nevertheless, it can lead to hemodynamic instability, higher levels of intra-operative blood loss, increased need for analgesics, and a higher incidence of postoperative nausea and vomiting. [7] Local anaesthetic agents such as bupivacaine, levobupivacaine, and ropivacaine are commonly employed in neuraxial anaesthesia. [8]

Bupivacaine is a widely used local anaesthetic known for its prolonged duration of action and favorable sensory-to-motor block ratio. However, its toxicity, especially at higher doses or during extended infusions for postoperative analgesia, remains a significant concern. As a result, ropivacaine, a newer long-acting amide local anaesthetic, was developed to offer a better safety profile. [9] Pavitra et al compared intrathecal isobaric 0.5% bupivacaine and isobaric 0.75% ropivacaine in patients undergoing lower abdominal surgeries and concluded that ropivacaine can be a better alternative to bupivacaine with faster recovery of motor functions providing early ambulation.[10]  A randomised and double blinded study was conducted by Kalbande et al comparing the efficacy of intrathecal hyperbaric 0.5% bupivacaine and 0.75% ropivacaine in patients undergoing infraumbilical surgeries and observed that at an equipotent dose hyperbaric ropivacaine demonstrated similar efficacy and safety when compared to hyperbaric bupivacaine (0.5%), while also offering enhanced motor recovery outcomes [11]

In order to hasten the time of onset and prolong the duration of analgesia, various adjuvants like dexamethasone, clonidine, opioids etc have been used intrathecally with local anesthetics. [12] Dexmedetomidine, an alpha-2 agonist, exhibits a combination of sedative, anxiolytic, hypnotic, pain-relieving, and sympatholytic effects. [13] A randomised double blind trial   was conducted by Gupta et al to evaluate the effects of intrathecal administration of 5 mcg of dexmedetomidine with 3 ml of isobaric ropivacaine 0.75% in patients undergoing lower limb surgeries and observed that the sensory and motor blockade were significantly prolonged on adding dexmedetomidine.[14] Singh at al compared two different doses of dexmedetomidine (5mcg, 10mcg) as adjuvant to 0.75% isobaric ropivacaine in patients undergoing lower abdominal surgeries and it was found that dexmedetomidine significantly augmented the duration of blockade without any side-effects. [15]

Compared to systemic use, intrathecal administration of opioids provides effective analgesia with fewer central and systemic adverse effects. Also they facilitate early ambulation in patients due to their sparing effects on sympathetic and motor functions. The most widely used intrathecal opioids are mu receptor agonists, which deliver significant pain relief but are also associated with various mu-related side effects. Acting as an agonist at kappa receptors, nalbuphine provides effective pain relief during and after surgery, while it’s antagonistic action at mu receptors minimizes the typical mu-mediated side effects. [16] Dessai et al conducted a prospective randomised controlled trial in patients undergoing endoscopic urological surgeries receiving intrathecal nalbuphine (1.5mg) with hyperbaric bupivacaine 0.5% (15mg) versus hyperbaric bupivacaine 0.5% (15mg) alone and concluded that nalbuphine provides prolonged postoperative analgesia with minimal side effects. [16] Borah et al also compared different doses (0.4, 0.8 and 1.6mg) of intrathecal nalbuphine with isobaric ropivacaine 0.75% in patients undergoing elective lower limb surgeries and observed that when used intrathecally, nalbuphine can effectively extend postoperative analgesia with minimal side effects, making it a strong alternative to other opioids. Additionally, adding nalbuphine to isobaric 0.75% ropivacaine improves pain management and accelerates motor recovery. [17]

Nagaraj et al conducted a prospective, randomised and double blinded study in patients undergoing orthopedic surgeries comparing the effects of intrathecal dexmedetomidine (10mcg) versus nalbuphine (1.5mg) as adjuvants to hyperbaric bupivacaine o.5% and observed that dexmedetomidine enhances the effectiveness of intrathecal bupivacaine greater than that of nalbuphine, without causing significant adverse effects [18] A randomised and double blinded study conducted by Khare et al on intrathecal dexmedetomidine(10mcg) versus nalbuphine(1mg) as adjuvants to hyperbaric bupivacaine 0.5% in patients undergoing lower abdominal surgeries proved dexmedetomidine to be a better adjuvant when compared to nalbuphine by prolonging the duration of blockade and the duration of analgesia. Also no hemodynamic variability/ side-effects were noticed [1].

Very few studies have been done on intrathecal dexmedetomidine versus nalbuphine as adjuvants to hyperbaric ropivacaine. Results of our study were comparable with that of above mentioned studies. Dexmedetomidine led to a rapid onset of sensory (7.93 min) and motor (4.2 min) blockade, whereas nalbuphine took significantly longer, with sensory and motor blockades occurring at 46.28 min and 26.38 min, respectively. The duration of sensory (647.38 minutes) and motor (524.88 minutes) blockade was significantly longer with dexmedetomidine compared to nalbuphine, which lasted 516.75 minutes and 265.5 minutes, respectively. In the dexmedetomidine group, the highest sensory blockade was observed at the T4 and T6 levels in 12.8% and 87.5% of cases, respectively, while in the nalbuphine group, 10% reached the T4 level and 90% reached the T6 level. Total duration of analgesia was significantly prolonged on adding dexmedetomidine (660.825 min) than nalbuphine (567.5 min). Hemodynamic variables remained constant in both the groups without any side-effects. Very few studies have been done on intrathecal dexmedetomidine versus nalbuphine as adjuvants to hyperbaric ropivacaine. Results of our study were comparable with that of above mentioned studies. Dexmedetomidine led to a rapid onset of sensory (7.93 min) and motor (4.2 min) blockade, whereas nalbuphine took significantly longer, with sensory and motor blockades occurring at 46.28 min and 26.38 min, respectively. The duration of sensory (647.38 minutes) and motor (524.88 minutes) blockade was significantly longer with dexmedetomidine compared to nalbuphine, which lasted 516.75 minutes and 265.5 minutes, respectively. In the dexmedetomidine group, the highest sensory blockade was observed at the T4 and T6 levels in 12.8% and 87.5% of cases, respectively, while in the nalbuphine group, 10% reached the T4 level and 90% reached the T6 level. Total duration of analgesia was significantly prolonged on adding dexmedetomidine (660.825 min) than nalbuphine (567.5 min). Hemodynamic variables remained constant in both the groups without any side-effects.

Dexmedetomidine, when used as an intrathecal adjuvant to hyperbaric ropivacaine, was found to significantly prolong sensory and motor block, deliver effective postoperative analgesia, and ensure stable hemodynamic with fewer side effects compared to nalbuphine.

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