European Journal of Cardiovascular Medicine

The definition of spinal anesthesia is "regional anesthesia achieved by blocking nerves in the subarachnoid space." This method is widely employed and well-liked all around the world. The benefits of an awake patient, low medication costs, a modest dose of the anesthetic, a quick beginning of action, comparatively few side effects, dependable surgical analgesia, and adequate muscular relaxation are all diminished by the typical disadvantage of a short duration of action. Intrathecal bupivacaine has an effect that lasts between 60 and 120 minutes. One way to extend the duration of action of intrathecal hyperbaric bupivacaine (0.5%) in spinal anesthesia is to add other medications, such as alpha-2 agonists like clonidine and dexmedetomidine, opioids like butorphanol, fentanyl, and sufentanyl, and anticholinergics like neostigmine.[1,2].

Post-operative analgesia is another benefit of using adjuvants. Butorphanol is a partial agonist at the kappa opioid receptor and a competitive antagonist at the mu opioid receptor. It produces analgesia without the adverse effects associated with mu receptors by binding to the kappa receptor in the brain and spinal cord, which is in charge of nociception. Butorphanol has a lesser propensity for misuse than other opioid medications, which explains its greater availability. Kappa-agonism also causes dysphoria at therapeutic or supertherapeutic dosages.[3]

Alpha 2 agonists like clonidine enhance the sensory and motor blockage of local anesthetics. The activation of postsynaptic alpha 2 receptors in the spinal cord's substantia gelatinosa mediates the analgesic effect after intrathecal injection. It increases the conduction block of local anesthetics and blocks the conduction of the Ad and C fibers.[4,5]

The Indian populace has produced a small amount of literature in recent years. Therefore, the purpose of this study was to assess the effects of butorphanol 0.2 mg and intrathecal clonidine 30 mcg as additives to 3 ml of 0.5% hyperbaric bupivacaine for spinal anesthesia.

Study design: Prospective randomised controlled study

       Inclusion Criteria:

• ASA physical status 1 and 2
• Patients in the age group of 18-60yrs
• Weight between 50- 70 kgs
• Height between 150-180 cms
• Patients with valid informed consent

  Exclusion criteria:

• Patients not giving consent
• Patient belonging to ASA grade 3 and 4
• Patients with gross spinal abnormality, localized skin infection, sepsis, haemorrhage is diathesis or neurological diseases
• Patients on anti-coagulant therapy
• Patients physically dependant on alpha 2 agonists and opioids
• Patients with history of drug allergy
•  
• Patients with cardiac, pulmonary, hepatic or renal disorders
• Patients below 18yrs of age and above 60 yrs of age

Methodology

 After obtaining the approval of scientific and ethics committee of government medical college Nizamabad and written informed consent, a total of 100 patients undergoing elective lower extremity orthopaedic surgeries under sub arachnoid block were selected. These patients were randomly assigned using computer generated charts to either of the two groups Patients belonging to the group BB was given 3 cc of 0.5% hyper baric bupivacaine (15mg)+ 0.2mg of Butorphanol (0.2CC) (butorphanol ampule consists of 1mg in 1ml).

Patients belonging to the group BC was given 3cc of 0.5% hyper baric bupivacaine (15mg)+30mcg (0.2CC)of clonidine (clonidine ampule consists of 150mcg in 1 ml)

Standard monitoring was carried out in the form of pulse oximetry, ECG and non-invasive arterial blood pressure monitoring. Pulse rate, Urine output respiratory rate, blood pressure, oxygen saturation were recorded every 5mins for first 30mins, every 10mins for next half an hour and then every 15mins till end of surgery

Total of 100 patients included fulfilling inclusion criteria. The mean age between the groups was comparable with no significant difference. Group BB included patients receiving 0.5% hyper baric bupivacaine (15mg) + 0.2mg of Butorphanol and group BC included patients receiving 0.5% hyper baric bupivacaine (15mg) + 30mcg of Clonidine.

Table 1: Comparison Of Mean Age Between The Groups

Figure 1: Comparison Of Mean Age Between The Groups

Table 2: Comparison Of Gender Distribution Between The Groups

Gender distribution between the groups, there was no significant difference.

Figure 2:Comparison Of Gender Distribution Between The Groups

Table 3: Comparison Of The Weight And Height Between The Groups

There is no significant difference in the mean weight and height of the participants between the group.

Figure 3: Comparison Of The Weight Between The Groups

Figure 3: Comparison of the height between the groups

Table 4: Comparison Of Distribution Of ASA Between The Groups

The distribution of ASA group, there is no significant difference in distribution between the groups.

Figure 4: Comparison Of Distribution Of ASA Between The Groups

Figure 5: Comparison Of Distribution Of ASA Between The Groups Table 5: Comparison Of Mean Duration Of Surgery Between The Groups

There Is No Significant Difference In The Mean Duration Of Surgery Between The Groups.

Figure 5: Comparison Of Mean Duration Of Surgery Between The Groups

Table 6: Comparison Of The Maximum Sensory Level Reached Between The Groups

There is similar maximum sensory level reached between the groups.

Figure 6: Comparison Of The Maximum Sensory Level Reached Between The Groups

Since spinal anesthesia, often referred to as subarachnoid block, provides quick onset, dependable anesthesia, and postoperative analgesia, it is a commonly used method in contemporary anesthesia practice for a variety of surgical operations. By adding adjuvants to the local anesthetic solution, spinal anesthesia can be made more effective and last longer. The ability of clonidine and butorphanol to extend the duration of sensory and motor blocking has drawn attention among these adjuvants, perhaps leading to better postoperative pain control.

An alpha-2 adrenergic agonist called clonidine modulates pain transmission centrally in the spinal cord, causing sensory block and sustained analgesia. On the other hand, the central nervous system's opioid receptors allow butorphanol, a mixed opioid agonist-antagonist, to produce its analgesic effects. Although butorphanol and clonidine have both been studied as intrathecal hyperbaric bupivacaine additions, there aren't many comparison studies that can clarify their respective safety and effectiveness profiles. Optimizing perioperative anesthesia and pain management techniques requires an understanding of the various effects of these adjuvants. The quality and duration of intraoperative anesthesia and postoperative analgesia can be greatly impacted by the adjuvant selection in spinal anesthesia. Thus, it is imperative to compare and rigorously assess the effects of several adjuvants, including butorphanol and clonidine, when together with hyperbaric bupivacaine administered intrathecally.

One hundred patients met the requirements for inclusion. Patients in group BC received 0.5% hyperbaric bupivacaine (15 mg) with 30 mcg of clonidine, whereas patients in group BB received 0.5% hyperbaric bupivacaine (15 mg) plus 0.2 mg of butorphanol. There was no discernible difference in the mean age across the groups. There was no discernible change in the groups' gender distribution. The individuals' mean height and weight do not significantly differ from one another. The distribution of the ASA group shows no discernible variation from the other groups. In line with the current study, Gupta K et al. discovered that there was no significant difference in the physical characteristics, such as mean age, gender distribution was male preponderance, and ASA was equivalent across the group.

Comparable mean age, gender distribution, ASA grade, physical characteristics, and surgery duration were recorded between the groups in a research identical to the one conducted by Ruku et al. Heart rate, systolic and diastolic blood pressure, and other hemodynamic measures were consistent and similar in both groups. (p>0.05) According to the current study, Gupta K et al. discovered that the groups' hemodynamic parameters—such as blood pressure and heart rate—were similar.45 Ruku et al.'s study, which is comparable to the one being conducted now, showed no discernible differences in the groups' mean arterial pressure, blood pressure, or heart rate.46 In contrast to utilizing bupivacaine alone, the addition of butorphanol to bupivacaine in spinal anesthesia helped preserve hemodynamic stability throughout surgery, according to a research by Nag S et al. Although no significant Although there have been reports of neurological issues, more extensive research is required to completely evaluate any possible negative short- or long-term impacts. The groups' mean surgical times do not differ significantly from one another.

The highest sensory level attained by each group is comparable. It was discovered that the groups' mean times for the beginning of sensory level T10 were similar. Patients in group BC had a significantly shorter time for two segment regression sensory level than patients in group BB. (p<0.05) those in group BC experienced a significantly shorter mean length of sensory block regression to the S2 section than those in group BB. (p<0.05) The mean start of motor blockade does not differ substantially, however group BC had motor blockade for a much longer period of time than group BB. (p<0.05).

In terms of sensory block regression and duration, motor blockade duration, and time to initial analgesic demand, intrathecal clonidine in combination with bupivacaine, a local anesthetic, proved to be more effective than butorphanol in this investigation. Nonetheless, the frequency of adverse effects and hemodynamic stability were similar in both groups. Thus, in some therapeutic situations, intrathecal clonidine seems to be a viable adjuvant for improving spinal anesthesia

1. Ganesh M, Krishnamurthy D. A Comparative Study of Dexmedetomidine and Clonidine as an Adjuvant to Intrathecal Bupivacaine in Lower Abdominal Surgeries. Anesth essays Res. 2018;12(2):539–45.
2. Gupta R, Verma R, Bogra J, Kohli M, Raman R, Kushwaha JK. A Comparative study of intrathecal dexmedetomidine and fentanyl as adjuvants to Bupivacaine. J Anaesthesiol Clin Pharmacol. 2011;27(3):339–43.
3. Shah VD, Bhavsar GM, Sirohi J, Mulani AJ, Shah DH. Comparative Study of Butorphanol versus Clonidine as an Adjuvant to Intra Thecal Hyperbaric Bupivacaine 0.5% For Lower Abdominal and Lower limb Surgeries. J Evol Med Dent Sci. 2020;9(52):3956–63.
4. Chopra P, Talwar V. Low dose intrathecal clonidine and fentanyl added to hyperbaric bupivacaine prolongs analgesia in gynecological surgery. J Anaesthesiol Clin Pharmacol. 2014;30(2):233–7.
5. Singh RB, Chopra N, Choubey S, Tripathi RK, Prabhakar, Mishra A. Role of Clonidine as adjuvant to intrathecal bupivacaine in patients undergoing lower abdominal surgery: A randomized control study. Anesth essays Res. 2014;8(3):307–12.
6. Ruetsch YA, Böni T, Borgeat A. From cocaine to ropivacaine: the history of local anesthetic drugs. Curr Top Med Chem. 2001;1(3):175–82.
7. Olawin AM. Spinal anesthesia. StatPearls . 2022. p. 1–10.
8. Kamel I, Ahmed MF, Sethi A. Regional anesthesia for orthopedic procedures: What orthopedic surgeons need to know. World J Orthop. 2022;13(1):11–35.
9. Ganapathy MK, Reddy V, Tadi P. Neuroanatomy, Spinal Cord Morphology. [Updated 2022 Oct 24]. In: StatPearls Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://ncbi.nlm.nih.gov/books/NBK545206/
10. Khan YS, Lui F. Neuroanatomy, Spinal Cord. In: StatPearls . StatPearls Publishing; 2022.
11. Hirabayashi S. Ossification of the ligamentum flavum. Spine Surg Relat Res. 2017;1(4):158–63
12. Ghannam JY, Al Kharazi KA. Neuroanatomy, cranial meninges. Stapearls. 2019
13. Jones MD, Newton          Inadvertent          extra-arachnoid   injections             in      myelography.      Radiology. 1963;80(5):818–22.
14. Shafique S, Rayi A. Anatomy, head and neck, subarachnoid space. StatPearls. StatPearls Publishing, Treasure Island; 2022.
15. Adeeb N, Mortazavi M, Deep D, Griessenauer C, Watanabe K, Shoja M, et al. The pia mater: A comprehensive review of literature. Child s Nerv Syst. 2013;29.
16. Cohen EN. Distribution of local anesthetic agents in the neuraxis of the dog. In: The Journal of the American Society of Anesthesiologists. The American Society of Anesthesiologists; 1968. p. 1002–11.
17. Chambers WA, Littlewood DG, Edstrom HH, Scott DB. Spinal anaesthesia with hyperbaric bupivacaine: effects of concentration and volume administered. BJA Br J Anaesth. 1982;54(1):75–80.
18. Axelsson KH, Edström HH, Sundberg AEA, Widman GB. Spinal anaesthesia with hyperbaric 0.5% bupivacaine: effects of volume. Acta Anaesthesiol Scand. 1982;26(5):439–45.
19. Yasaei R, Saadabadi A. Clonidine. In: StatPearls . StatPearls Publishing; 2021.
20. Groom MJ, Cortese S. Current Pharmacological Treatments for ADHD. Curr Top Behav Neurosci.2022;57:19–50.
21. Ommi D, Teymourian H, Zali A, Ashrafi F, Jabbary Moghaddam M, Mirkheshti A. Effects of Clonidine Premedication on Intraoperative Blood Loss in Patients With and Without Opium Addiction During Elective Femoral Fracture Surgeries. Anesthesiol pain Med. 2015 Aug;5(4):e23626.
22. Khakurel S, Sapkota S, Karki AJ. Analgesic Effect of Caudal Bupivacaine with or without Clonidine in Pediatric Patient. J Nepal Health Res Counc. 2019 Jan;16(41):428–33.
23. Byerley EM, Mohamed MW, Grindeland CJ, Muzzy Williamson JD. Neonatal Abstinence Syndrome Practices in the United States. J Pediatr Pharmacol Ther JPPT Off J PPAG. 2021;26(6):577–83.
24. Carpenter M, Berry H, Pelletier AL. Clinically Relevant Drug-Drug Interactions in Primary Care. Am FamPhysician. 2019 May;99(9):558–64.
25. Covino BG, Wildsmith JAW. Clinical pharmacology of local anesthetic agents. Neural blockade Clin Anesth Manag pain. 1998;3:97–128.
26. Miller RD, Pardo M. Basics of anesthesia e-book. Elsevier Health Sciences; 2011.
27. Vadhanan P, Tripaty DK, Adinarayanan S. Physiological and pharmacologic aspects of peripheral nerve blocks. J Anaesthesiol Clin Pharmacol. 2015;31(3):384–93.
28. Sekimoto K, Tobe M, Saito S. Local anesthetic toxicity: acute and chronic management. Acute Med Surg. 2017;4(2):152–60.
29. Hoofnagle JH. LiverTox: a website on drug-induced liver injury. In: Drug-induced liver disease. Elsevier; 2013. p. 725–32.
30. Pathan H, Williams J. Basic opioid pharmacology: an update. Br J pain. 2012;6(1):11–6.