European Journal of Cardiovascular Medicine

Levobupivacaine is an optical isomer of bupivacaine of the amide class and is linked to a decreased risk of toxicity than either the dextro-enantiomer itself or the racemic bupivacaine [2, 3] Levobupivacaine slows the transmission of the action potential in neurons that regulate sensory, motor, and sympathetic activity, as it does with all local anaesthetics. [1] Other excitable tissues like the heart and the central nervous system are also affected by this interaction, leading to consequences on the heart and nervous system. Levobupivacaine, like bupivacaine, has a long half-life and can be used in various anaesthetic procedure. Its onset of action is about fifteen minutes. Duration of action is dose dependent and varies with anaesthetic procedure used. In all

comparative study, encompassing those of epidural, peripheral neuron block, local infiltration, and peri-bulbar injection, the analgesic effects of levobupivacaine appear to be substantially equivalent in comparison to bupivacaine at the same dose. [4–7 Levobupivacaine generates less prolonged motor blockade than sensory blockade when injected in the epidural area. [4, 5]. perioperative epidural analgesia provides physiological advantages that may lessen perioperative complications and enhance postoperative outcome. [9-11]Adjuvants such as fentanyl, ketamine or dexmedetomidine lessen the overall dose requirement of local anaesthetic and lengthen the duration of sensory-motor block. Adjuvant co-administration may enhance peri-neural block effectiveness and lessen the toxicity of local anaesthetics. To achieve a strong anaesthetic effect, a variety of opioids, including fentanyl, have been utilized as an adjunct for epidural injection in conjunction with local anaesthetic medications. [12] Dexmedetomidine is highly selective alpha 2 adrenergic agonist having analgesic, sympatholytic and sedative action that acts on presynaptic and postsynaptic sympathetic nerve endings as well as the central nervous system to reduce the discharge of sympathetic neurons and norepinephrine release. In light of the advantages of levobupivacaine and other adjuvants, this randomized trial was taken into consideration in order to compare the clinical effects of fentanyl and dexmedetomidine in conjunction with epidural levobupivacaine for lower limb orthopaedic procedures.

Objectives:

• To assess the effectiveness of the post-operative epidural analgesia of Levobupivacaine with Dexmedetomidine and Levobupivacaine with Fentanyl in orthopaedic surgeries.
• To assess further need of analgesia while using two different adjuvants with Levobupivacaine in post-operative period.
• To assess the hemodynamic effects of two different adjuvants with Levobupivacaine.
• To assess the side effects.

Study Design: Randomized double blinded controlled trial

Study Site: Department of Anaesthesiology and Critical Care, Nalanda Medical College & Hospital, Patna, Bihar

Study Duration: 2 Years

Source of Data:  ASA Grade I and Grade II patients of both sexes between 18 to 65 years undergoing lower limb orthopaedic surgery under regional anaesthesia.

Ethical Consideration:

The study protocol was approved by the institutional ethics committee of NMCH, Patna and complied with International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki. Informed consent was taken from patients before surgery. Participant Information Sheet (PIS) was provided and explained to patients in their local language. Thereafter, consent was approved by taking their signature or thumb impression on the informed consent form. The data were obtained from the hospital record system after appropriate approval from the concerned authorities.

Sample Size: A total of 60 patients were recruited into the study with 30 patients in each group.

Inclusion criteria:

• Patient of either sex
• Patients of ASA Grade I and II
• Patients of age 18-65 years
• Patient undergoing lower limb orthopaedic surgery under regional anaesthesia of duration ≥ 2 hours. Drug used in epidural anaesthesia is either D or F.

Exclusion criteria:

• Patient refusal
• Known allergy to local anaesthetics
• Local infection at the proposed site
• Any coagulopathy

30 patients in group I received (10 ml of 0.125% levobupivacaine + .5 mcg/kg dexmedetomidine) and 30 patients in group II received (10 ml of 0.125% levobupivacaine + 1 mcg/kg fentanyl) for epidural analgesia.

In this randomised double blinded controlled trial, our goal was to find suitable adjuvant to Levobupivacaine for controlling of post-operative pain under epidural technique. We found that dexmedetomidine was better adjuvant to levobupivacaine as compared to fentanyl. However, haemodynamic parameters were more stable in fentanyl group. The findings supporting this result are discussed below. Time of peak analgesia and duration of analgesia were significantly greater in dexmedetomidine group. Number of top-ups were significantly greater in fentanyl group. VAS scores were significantly lower in dexmedetomidine group at 10, 20 and 30 minutes. However, VAS scores were significantly less in fentanyl group after 12 hours. Respiratory rate was significantly lower in fentanyl group as compared to dexmedetomidine group at 4, 8 and 12 hours. Significantly greater degree of sedation was noticed among fentanyl groups at 20 minutes, 4 hrs, 16 hrs, and 24 hrs. Heart rate was significantly lower in dexmedetomidine group as compared to fentanyl group. SBP as well as DBP was significantly lower in dexmedetomidine group as compared to fentanyl group. Dexmedetomidine exhibits sympatholytic and hemodynamic stability properties, making it an extremely selective α2 agonist [108]. It causes blood pressure as well as heart rate to drop in a dose-dependent manner [13]. According to earlier research, dexmedetomidine reduces

central sympathetic outflow, which lowers serum levels of norepinephrine as well as adrenaline and regulates the stress reaction to intubation [14]. Dexmedetomidine has been found in numerous studies involving patients enduring general or gynaecological surgery to reduce the cardiovascular reaction to intubation. These results coincide with accordance with our study's findings, which revealed a marked decline in the shift in HR, SBP, as well as DBP [15, 16. Up to 40% of healthy surgical patients experienced postoperative bradycardia as a result of high dose patients. These were typically transient symptoms that were effectively managed with atropine as well as epinephrine. Bradycardia and hypotension can result from a dexmedetomidine-induced cardiovascular depression. Bradycardia results from the activation of either imidazoline-preferring receptors, alpha-2-adrenoceptors, or combination in the ventrolateral medulla. It might be related to our patients' sluggish bolus infusion.

1. Cristwood RW, Greaves JL. Levobupivacaine: a new safer long acting local anaesthetic agent. Expert Opin Invest Drug. 1999; 8:861-76.
2. Denson DD, Behbehani MM, Gregg RV. Enantiomerspecific effects of an intravenously administered arrythmogenic dose of bupivacaine on neurons of the nucleus tractus solitarius and the cardiovascular system in the anesthetized rat. Reg Anesth. 1992;17:311-6.
3. Mazoit JX, Boico O, Samii K. Myocardial uptake of bupivacaine. Pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the isolated perfused rabbit heart. Anesth Analg. 1993;77:477-82.
4. Cox CR, Faccenda KA, Gilhooly C. Extradural S(-)- bupivacaine: comparison with racemic RS-bupivacaine. Br J Anaesth. 1998;80:289-93.
5. Cox CR, Checketts MR, MackKenzie N. Comparison of S(-)-bupivacaine with racemic (RS)-bupivacaine in supraclavicular brachial plexus block. Br J Anaesth. 1998;80:594-8.
6. Mc Lure HA, Rubin AP. Comparison of 0.75% levobupivacaine with 0.75% racemic bupivacaine for peribulbar anaesthesia. Anaesthesia. 1998;53:1160-4.
7. Kingsnorth AN, Cummings CG, Bennett DH. Local anaesthesia in elective inguinal hernia repair: a randomised, double-blind study comparing the efficacy of levobupivacaine with racemic bupivacaine. Eur J Surg. 2002;168:391-6
8. Shukla U, Singh D, Singh J, Yadav JBS. Comparative Study of Epidural Dexmedetomidine, Fentanyl, and Tramadol as Adjuvant to Levobupivacaine for Lower Limb Orthopedic Surgeries. Cureus. 2022 May 22;14(5):e25225. doi: 10.7759/cureus.25225. PMID: 35747019; PMCID: PMC9213781.
9. Stewart J, Kellett N, Castro D. The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy volunteers. AnesthAnalg. 2003; 97:412-6.
10. Foster RH, Markham A. Levobupivacaine. A review of its pharmacology and use as a local anaesthetic. Drugs. 2000; 59:551-79.
11. Benzon HT, Wong HY, Belavic AM Jr, Goodman I, Mitchell D, Lefheit T, Locicero J. A randomized double-blind comparison of epidural fentanyl infusion versus patient-controlled analgesia with morphine for postthoracotomy pain. AnesthAnalg. 1993; 76:316-22.
12. Tanskanen PE, Kyttä JV, Randell TT, Aantaa RE. Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumour surgery: Adouble-blind, randomized and placebo-controlled study. Br J Anaesth. 2006;97:658–65.
13. Tanskanen PE, Kyttä JV, Randell TT, Aantaa RE. Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumour surgery: Adouble-blind, randomized and placebo-controlled study. Br J Anaesth. 2006;97:658–65.
14. Talke P, Chen R, Thomas B, Aggarwal A, Gottlieb A, Thorborg P, et al. The haemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anaesth Analg. 2000;90:834–39.
15. Aho M, Erkola O, Kallio A, Scheinin H, Korttila K. Dexmedetomidine for maintenance of anaesthesia in patients undergoing abdominal hysterectomy. AnaesthAnalg. 1992;75:940–46.
16. Lawrence CJ, De Lange S. Effect of single preoperative dexmedetomidine dose on isoflurane requirements and peri-operative haemodynamic stability. Anaesthesia. 1997;52:736–44.