A Comparative Perspective Study between Intrathecal Midazolam & Nalbuphine as an adjuvant with Hyperbaric Bupivacaine for Post-Operative Analgesia in Total Abdominal Hysterectomy

Background: Subarachnoid block is the preferred form of regional anesthesia for obstetric surgeries. Local anesthetic agents alone are insufficient in providing adequate postoperative analgesia, which is an essential factor for the patients & is the sole essence of anesthesia. Adding adjuvant will result in better quality, the efficacy of SAB & will prolong analgesia postoperatively. Due to minimal hemodynamic & respiratory complications, Nalbuphine, an opioid, can be favored as an adjuvant to subarachnoid block. The addition of Nalbuphine in limiting doses to Hyperbaric Bupivacaine offers improved block quality & adequate pre & post-operative analgesia. Midazolam, an imidazobenzodiazepine given intrathecally, raises the threshold of pain; it also has hypnotic, anticonvulsant, muscle relaxant & amnesic effects of other benzodiazepines. Objectives: Primarily to compare the duration of pain relief in the postoperative period between administration of Intrathecal Nalbuphine (1mg) & Midazolam(2.5mg) ( Timing of 1 st rescue Study Protocol Dubey et al.; JPRI, 33(60B): 918-925, 2021; Article no.JPRI.80207 919 analgesia). Secondarily to compare the onset of action & duration of motor & sensory block (Modified Bromage Scale), Effect on Hemodynamic Parameters, 24 hours requirement of analgesic (No. of Injection Paracetamol 15-20mg/kg ), Degree of sedation(Modified Ramsay Sedation Scale) & After-effects(PONV, Pruritis, Shivering & Retention of urine). Methodology: The study type will be a Comparative Prospective Study on 60 ASA 1 & 2 females in the age group 35-75 years, planned for total abdominal hysterectomy will be separated in two equivalent Group M (n=30) & Group N (n=30). Group M will receive combination Midazolam preservative-free 0.5 ml (2.5 mg) with 0.5% Hyperbaric Bupivacaine 2.5 ml(12.5 mg), & Group N will receive combination Nalbuphine 1 ml (1 mg) with Hyperbaric Bupivacaine (0.5%) 2.5 ml (12.5mg) by Intrathecal Route. Analgesia duration in the postoperative period, the onset of action & duration of motor & sensory block, effect on hemodynamic parameters, 24 hours analgesics requirement, degree of sedation, after-effects, if any, will be studied & compared. Conclusion: Expected to prove the hypothesis that adding which of the following adjuvant 1mg Nalbuphine or 2.5mg Midazolam with 0.5% Hyperbaric Bupivacaine intrathecally given in SAB prolongs the postoperative analgesia duration more as compared to other.


INTRODUCTION
Subarachnoid block was introduced about a hundred years ago & is still the most popular regional anesthesia approach. But, the local anesthetic drugs (whether isobaric or hyperbaric) used for subarachnoid block do not prolong postoperative pain relief. Anaesthesiologists face this struggle as they oversee peri & postoperative pain control [1]. Excessively soaring regional blocks & toxicity due to local anesthetics are the most common reasons for deaths linked to regional blocks; therefore, decreasing dosage of local anesthetics, adding adjuvants, usage of latest methodology to circumvent inordinate blocks, & superior tackling of local anesthetic toxicity are the novel targets for reducing death rate linked to regional anesthesia [2].
The subarachnoid block is a preferred technique of anesthesia as it is easy to carry out, the outset of action is rapid, better relaxation of muscle & effectual. Additionally, reduced recovery time, quick return of patient's average oral intake & safety are its added advantages. Analgesia in the postoperative phase is essential to provide comfort & reinstatement of functions effectively; it is one of the primary concerns of all patients [3,4]. Though subarachnoid block is relatively safe, its duration of action is short. To overcome this snag, various adjuvants are being added per usual. Subarachnoid block with Hyperbaric Bupivacaine 0.5 Percent, along with adjuvants, is consistently administered for lower abdomen surgeries.
Nalbuphine, an opioid, has mixed kappa-agonist & mu-antagonist properties. It acts by competitively displacing other mu-agonists from the receptor site (mu-antagonism). Also, its binding to kappa-receptors produces an agonist effect. Due to this mixed pattern of agonism & antagonism, Nalbuphine is a mixed kappaagonist-mu-antagonist. It has minimal respiratory depression, in contrast to other opioid analgesics acting centrally because it has mixed partial kreceptor agonist &μ-receptor antagonist activity [8,9].

Midazolam
is a water-soluble imidazobenzodiazepine derivative. Midazolam is similar to other benzodiazepines in binding extensively to plasma proteins. Midazolam has hypnotic, anticonvulsant, muscle relaxation & amnesic effects of other benzodiazepines [10,11].

Research Question
Which is more effective among Midazolam 2.5 mg & Nalbuphine 1 mg when used as an Intrathecal Adjuvant to Hyperbaric Bupivacaine in providing analgesia in the post-operative phase?

Rationale
Numerous studies have been conducted about the individual strength of both drugs. We want to compare which adjuvant is better when administered intrathecally along with Hyperbaric Bupivacaine {0.5%} 2.5 ml (12.5mg). Hence the motive of the study.

Aim
The study aims to compare the Efficacy of midazolam & nalbuphine when they are added as an Adjuvant with Hyperbaric Bupivacaine {0.5%} intrathecally in patients planned for Total Abdominal Hysterectomy.

Secondary
Comparison of 1) The onset of action & duration of motor & sensory block.
2) The effect on hemodynamic parameters.
3) 24-hour requirement of analgesic(Paracetamol 15-20 mg/kg) 4) Degree of sedation. 5) After-effects(PONV, pruritus, shivering, retention of urine & Any Other) Baseline values will be recorded 2. An i.v access will be established with an 18 gauge IV cannula. 10ml/kg of RL will be used to preload. 3. premedication with injection ondansetron 75-100 µ/kg iv shall be done 10 minutes before the SAB procedure. 4. SAB will be performed at intervertebral space L3-L4 with 25G Quincke needle using the median approach in the left lateral or sitting position following all aseptic measures. The drug will be injected after clear, free-flowing cerebrospinal fluid (CSF) is observed.

Study Design
Following the procedure patient shall be quickly shifted to a prone position. Supplemental oxygen will be given using Hudson's mask at 4 L/min.

5.
Parameters to be recorded are: After that, the Sensory Block will be examined every 2 minutes until the Maximum Sensory Blockade is achieved.

Sensory Block-Onset and Duration
• Onset is the period between anesthesia injection and sensory block at T10 dermatome.
• Duration -(assessed by two-segment regression) is the period between injection of anesthesia and the decrease of maximum sensory block level by two segments.

Motor Block
Assessment of the quality of motor blocks will be carried out using a modified Bromage scale.
• Monitoring hemodynamic parameters every 2 mins for initial 10 mins, every 5 mins for the next 30 mins & finally every 15 mins until the surgery is completed. • If heart rate reduces to 20 percent below baseline, injection glycopyrrolate will be administered & if the blood pressure falls 20 percent below the baseline, injection mephentermine will be administered. • Patient will be shifted to the postoperative ward after surgery is completed. Monitoring, every half an hour for initial six hrs, will be done.
Later daily monitoring will be done. If the patient shows a VAS score of 4 or more, injection paracetamol 15-20 mg/kg i.v shall be administered as rescue analgesia.

Visual Analog Scale
• VAS will be described to the patient preoperatively.

LIMITATIONS
1 Drug given only by Intrathecal Route 2 This study will be limited to female patients undergoing total abdominal hysterectomy. 3 There is variation in pain threshold in between patients .

CONCLUSION
Adjuvant, Intrathecal Nalbuphine(1 mg), added to Hyperbaric Bupivacaine(12.5 mg) is expected to enhance the quality of block in comparation to (2.5 mg) Midazolam as an adjuvant to Bupivacaine. It is also expected for nalbuphine to provide 8-9 hours long postop analgesia when utilised in addition to bupivacaine, without producing noteworthy side effects in patients undergoing TAH under sub-arachnoid block.

CONSENT
As per international standard or university standard, patient's written consent has been collected and preserved by the author(s).

ETHICAL APPROVAL
As per international standard or university standard written ethical approval has been collected and preserved by the author(s).