1. Title of the project: Comparison of effects of 0.5% levobupivacaine heavy versus 0.5% bupivacaine heavy in patients undergoing transurethral resection of prostate under spinal anaesthesia.

2. Type of study: A prospective,single-blinded, randomized study

3. Aims and Objectives:

Primary Objectives:

To compare the effects of 2 ml of 0.5% levobupivacaine heavy and 2 ml of 0.5% bupivacaine heavy in patients undergoing transurethral resection of prostate under spinal anaesthesia by the following parameters:

a) Time taken for onset of sensory and motor blockade

b) Time taken to achieve a maximum sensory level

c) Time taken for 2-segment regression

d) Time taken for sensory and motor recovery

Secondary Objectives:

To compare the effects of 2 ml of 0.5% levobupivacaine heavy and 2 ml of 0.5% bupivacaine heavy in patients undergoing transurethral resection of prostate under spinal anaesthesia by the following parameters:

a) Hemodynamic changes

b) Frequency of adverse events

4. Justification for study: Spinal anaesthesia is a popular technique of anaesthesia in uro-genital surgeries. Many of the patients who undergo transurethral resection of the prostate are elderly and present with multiple co-morbidities. Marked hypotension may be detrimental especially in elderly with limited cardiac reserve. Spinal anaesthesia is well tolerated by this age group as it doesn’t involve airway manipulation or polypharmacy, provides good intra and post-operative analgesia and minimizes surgical blood loss while enabling swift identification of complications during transurethral resection of prostate (overhydration, water intoxication or bladder rupture).

Bupivacaine is a commonly used local anaesthetic in spinal anaesthesia. Due to its high affinity to plasma proteins, it does not elicit clinical signs of drug accumulating in the plasma until an advanced stage. Once the plasma protein binding sites are exhausted, the concentration of the drug increases rapidly and signs of toxicity manifest.

Levobupivacaine, an isomer of bupivacaine is less cardiotoxic as it has a low affinity for cardiac sodium channels and a high affinity for plasma proteins owing to the lower affinity of the S (−) isomer to cardiac sodium channels compared to the R isomer, it is associated with less cardiac side effects.

5. Departments involved: Department of Anaesthesiology, Kasturba Medical College, Manipal.

6. Study Period: The study will begin after obtaining approval from the Institutional Ethics Committee. The duration of the study will be from 2024 -2026 (2 years).

7. Sample Size: To be calculated after the pilot study

8. Materials and Methods: A prospective randomized control study will be done in patients undergoing transurethral resection of prostate under spinal anaesthesia.

Inclusion Criteria:

a) 50-75 years of age

b) BMI of 18-30 kg/m2

c) ASA I, II, III

Exclusion Criteria:

a) Unable to follow simple commands

b) Raised Intracranial pressure

c) Infection at the site of administration of spinal

d) Hypersensitivity to local anaesthetic

f) Coagulopathy

e) Sepsis

f) Uncorrected hypovolemia

Biological materials required: Nil

Statistical Methods: Numerical variables will be presented as mean & standard deviation (SD) and unpaired student-t test will be done. Categorical variables will be presented as percent and will be analysed using Pearson’s chi-square.A p-value of 5% will be considered significant.

Tools Used: Nil

9. Detailed description of procedure:

Observers: Observer 1: Anaesthesia faculty who is not otherwise involved in the study prepares the solution to be administered intrathecally based on the computer generated random number table allocation of the group.

Observer 2: Anaesthesiology postgraduate involved in the study (blinded to the drug given intrathecally) will record the onset of sensory and motor blockade, maximum level of sensory and motor block, time to recovery from sensory and motor blockade, haemodynamic parameters and any complications arising during the study period.

Randomization and Group Allocation:

Patients will be randomly allocated into one of the 2 groups using computer generated random number table.

Group L: (Group Levobupivacine): Patients in this group will receive 2 ml of 0.5% levobupivacaine intrathecally.

Group B: (Group Bupivacaine): Patients in this group will receive 2 ml of 0.5% hyperbaric bupivacaine intrathecally.

Both bupivacaine and levobupivacaine will be stored in room temperature in the OT storage room.

Procedure:

A detailed preoperative evaluation of the patient will be done one day prior to surgery by the anaesthesiology postgraduate. Written informed consent will be obtained and all patients will be kept nil per oral (6 hours for solids and 2 hours for clear fluids).

On the day of the surgery, the patient will be shifted to the operating theatre where standard monitors (pulse oximeter, non-invasive blood pressure and 5 lead Echocardiography) will be attached. The baseline heart rate, blood pressure and oxygen saturation will be recorded. An intravenous line will be secured with an 18 Gauge cannula and intravenous infusion of Ringer’s lactate will be started.

Patients will be positioned in the left lateral decubitus position. Under sterile precautions, spinal anaesthesia will be administered by observer 2 at the level of the L3 - L4 or L4 - L5 intervertebral space with 23 gauge Quincke- Babcock spinal needle. Once free flow of cerebrospinal fluid is obtained, the study drug will be injected intrathecally over a period of 10 seconds. Patients will be placed in the supine position immediately after intrathecal injection and the time of intrathecal drug injection will be noted as time zero “0”. Co-loading with Ringer Lactate solution will be started at a rate of 10ml/kg in the first hour.

A cold alcohol swab will be used to check appreciation of temperature. As pain and temperature sensations are both carried by A-delta fibres, the inability to appreciate cold sensation will be taken as a surrogate for analgesia. Check with the cold swab will be performed every 2 minutes along the midclavicular line on both sides. The higher of the two sides will be taken as the end point for this parameter.

Onset of analgesia at T10 will be noted. The sensory level will be checked every 2 minutes as described above until the level does not ascend any further for 4 consecutive readings. This dermatomal level will be noted as the highest level of analgesia. Sensory level will be checked every 5 minutes thereafter till the end of 30 minutes, and every 10 minutes thereafter till 2-segment regression (defined as recovery of sensory block by 2 segments from the highest level achieved in that patient) and sensory recovery (around S2-S4 segments) occur.

Motor blockade will be assessed by modified Bromage scale (0 = no paralysis, able to flex hip/knee/ankle; 1 = able to flex knee and ankle, unable to raise extended leg; 2 = able to flex ankle, unable to flex hip and knee; 3 = unable to flex hip, knee and ankle). Motor blockade will be evaluated at 2-minute intervals till a modified Bromage score of 3 is obtained or till maximum motor blockade is achieved. This time is noted as onset of motor blockade. The time at which ankle movement returns is noted to indicate recovery from motor blockade.

In case of requirement of rescue analgesia, spinal anaesthesia will be supplemented with analgesics as and when needed.

Blood pressure will be recorded every 5 minutes for the first half an hour and every 10 minutes thereafter. Hypotension after spinal anaesthesia will be defined as an absolute value of SBP less than 100mmHg, or a decrease in SBP by more than 20% of the baseline value or an absolute value of MBP less than 60mmHg. Episodes of hypotension will be treated using intravenous boluses of mephentermine 3 mg/ Ephedrine bolus of 6mg.

Heart rate will be recorded every 5 minutes for the first half an hour and every 10 minutes thereafter. A heart rate < 50/min will be considered as bradycardia but will be treated with atropine 0.6 mg only if associated with hypotension.

A respiratory rate less than 8/min or pulse oximetry values less than 95% on room air will be taken as significant and oxygen via face mask or nasal prongs will be supplemeted at 4L/minute.

Any adverse effects such as nausea, vomiting, shivering, pruritus will be noted and managed accordingly.

10. Potential risks and benefits: Standard risks pertaining to spinal anesthesia and transurethral resection of prostate.

Benefits: Drug giving better hemodynamic stability can be used in elderly patients

11. Ethical considerations and methods to address issues: The study requires approval from the Institutional Ethics Committee. lnformed consent will be obtained from the participants. Patients have the right to opt out of the study at any time during the study period with no compromise on their subsequent medical treatments and benefits to which they are entitled. No direct identifiers will be collected, hence ensuring confidentiality. Standard anaesthetic techniques will be used in all patients and strict asepsis will be followed.

12. Budget: Rs 5000

Patients will be compensated for the cost of 0.5 % bupivacaine heavy ( Rs 35) and 0.5 % levobupivacaine heavy (Rs110).