Comparison of efficacy of intrathecal fentanyl as an adjuvant to bupivacaine and ropivacaine in lower limb orthopaedic surgeries for post-operative analgesia

Background and rationale

The word “anaesthesia” is derived from the Greek word meaning “loss of sensation”. Insensibility to pain without loss of consciousness is defined as analgesia. Regional anaesthesia is the temporary elimination of pain and nerve transmission in specific body areas with local anaesthetic drugs without inducing unconsciousness. When comparing regional anaesthesia to general anaesthesia, the frequency of its use is increasing.^1,2 This is due to early mobilisation, the high analgesia level that can be achieved, diminished duration of hospital stays and lower post-operative nausea and vomiting.² In addition, due to the recent rise in the use of ultrasonography, regional anaesthesia techniques are performed more reliably and effectively.³ In order to conduct a procedure or intervention that is in the patient’s best interest and will aid both the patient and the healthcare system as a whole, regional anaesthesia techniques are frequently used. Patients, healthcare providers, and institutions place a high value outcome such as mortality, readmissions, care safety and efficacy, patient satisfaction, cost-care ratios and timeliness of care provided. Thus, the perioperative team must work to ensure the best outcome for each patient. Knowledge of outcomes, benefits and risks is essential for the patient to be able to provide informed consent as well. Regional analgesia techniques diminish the neuroendocrine response to stress, thromboembolic phenomena and the use of parenteral analgesics in the post-operative period. The duration of effective analgesia is determined by the dose and concentration of local anaesthetics. The greater the volume and concentration of the local anaesthetic agent, the higher the possibility of local anaesthetic systemic toxicity. Opioids, when added as adjuvants, prolong post-operative pain relief accompanied by improved quality of analgesia. However, their usage can lead to side effects such as urinary retention, sedation and pruritis.⁴

Sub-arachnoid block or spinal anaesthesia is a common mode of anaesthesia that is used for orthopaedic surgeries of the lower limb.⁵

The anaesthetic ropivacaine has a prolonged duration of action. It is an S-enantiomer amide⁶ that is enantiomerically pure and exhibits low lipid solubility and a high pKa. It inhibits Aδ and C nerve fibres that transmit pain more potently than Aβ fibres that regulate motor function. The effect of ropivacaine occurs via reversible inhibition of nerve impulse conduction by reducing cell membrane permeability to sodium ions.

Bupivacaine hydrochloride is a long-acting amide anaesthetic. It is a commonly used local anaesthetic drug in sub-arachnoid blocks.⁷ Its uses include as intraoperative local anaesthetic agent, post-operative analgesia and treatment of chronic pain. Bupivacaine’s mechanism of action is thought to be similar to that of other local anaesthetics, in that it prevents sodium ions from passing through the neuronal membrane and generating an action potential. In the exterior lipid layer of the neuronal membrane, competitive binding to calcium sites is hypothesised to take place, leading to secondary interference from mobile phosphate groups. Sodium ion passage is inhibited by preventing molecular membrane reconfiguration from the inactive state (sodium impermeable) to the active (sodium permeable) state.

Fentanyl is a synthetic opioid. It can be added as an adjuvant to local anaesthetic agents used intrathecally.⁸ Fentanyl has the notable characteristics of being rapidly eliminated from serum alongside having high potency. Additionally, it has the benefit of causing minimal histamine release. Due to its substantial tissue absorption, serum levels quickly decrease after reaching their peak concentrations, accompanied by decrease in levels in the brain. The analgesic effect of fentanyl lasts for 30 to 40 minutes.⁹ However, when administered in high doses, there is a possibility of a second peak of activity several hours later. This is due to the release of the bound drug from tissue reserves. The use of opioids as an adjuvant to local anaesthetic agents has a synergistic action on its sensory blockade effects without significantly affecting its sympathetic activity. Fentanyl is an adjuvant used extensively to local anaesthetic agents used intrathecally.

Ensuring the successful alleviation of pain is crucial for healthcare professionals attending to patients who are undergoing surgical procedures.¹⁰ Pain relief offers notable physiological advantages, which is why the assessment of pain management is progressively gaining importance as a measure of post-operative quality. The objective of managing pain after surgery is to minimize or eliminate discomfort and pain while keeping adverse effects to a minimum. The post-operative analgesic effects of fentanyl are well established. While bupivacaine is commonly used for lower limb orthopaedic surgeries, there is an increasing use of ropivacaine for the same.¹¹ This study will allow us to compare post-operative analgesia in the two groups of patients and the analgesic choice to make for lower limb orthopaedic surgeries to reduce the need for rescue analgesia in the post-operative period primarily. Secondary objectives will include comparison of the onset, duration of analgesia, and duration of sensory and motor blockade, haemodynamic stability of patients, the requirement of 24 hours rescue analgesia and incidence of side effects between both groups.

Objectives

Primary objective

To compare post-operative analgesia in patients receiving bupivacaine with fentanyl and ropivacaine with fentanyl in lower limb orthopaedic surgeries via Sub-arachnoid block.

Secondary objective

Study setting

The study will be conducted at Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (DMIHER), Acharya Vinoba Bhave Rural Hospital (A.V.B.R.H.).

Study design

Inclusion criteria

Exclusion criteria

Sampling size

The study will be carried out on 66 adult patients of both sexes (33 patients in each group) fulfilling all inclusion criteria. They will be divided into two group randomly:

Rationale for selected sample size

The sample size was calculated using the formula for sample size calculation from the difference of two means.

In order to calculate sample size for comparing two means, data inputted were

Ratio of sample size (Group 2/Group 1): 1

(Table 1)

Formula used for calculation of sample size:

n₁: sample size of group A n₂: sample size of group B

σ₁: standard deviation of group A σ₂: standard deviation of group B

Δ: difference in group means

K: ratio of n₁/n₂

Z_1-α/2: two-sided Z value

Z_1-β: power

Calculated sample size:

Group A: 33, Group B: 33

Total: 66

(Table 2)

Statistical analysis

SPSS version 15.0 will be utilised for data analysis. To determine statistical significance, a mean P value below 0.05 will be considered significant when represented graphically.

Methodology

Patients fulfilling the inclusion criteria and scheduled for lower limb orthopaedic surgeries will be explained the procedure following which informed and written consent will be obtained. A detailed history will be taken from patients, followed by a thorough general examination. The procedure will be explained to the consenting patients preoperatively. The selected patients will be kept fasted as per fasting guidelines prior to the scheduled day of operation. Vital parameters of the patients such as pulse rate, respiratory rate, oxygen saturation (SpO₂), blood pressure and electrocardiogram (ECG) will be recorded in the preoperative room. The selected patients will be divided into two random groups by use of a computer-generated table. Each group will consist of 30 patients each, group A with patients who will receive bupivacaine and fentanyl and group B with patients who will receive ropivacaine and fentanyl. Prior to the administration of anaesthesia, patients will be informed of the study and its techniques again. A Multipara monitor will be connected to the patient. Baseline readings of heart rate, blood pressure and oxygen saturation will be noted before the start of the procedure. The above-mentioned parameters will be recorded after anaesthesia administration. Patients will be coloaded with 2 mL/kg of Ringer lactate after securing intravenous access with a 20G I.V. cannula. The procedure will be confirmed, and the patient will be explained the technique again. Under all aseptic precautions, sub-arachnoid block will be given with the patient in sitting/lateral position. 25G Quincke needle will be introduced in L3-L4 interspace. Bupivacaine 3 mL with fentanyl 25 μg for group A and ropivacaine 3 mL with fentanyl 25 μg with fentanyl for group B will be administered. The patient will be immediately made supine, following which the table orientation will be adjusted for the block to reach a spinal level of T12. The onset of sensory anaesthesia will be checked with pinprick method. Quality of motor block will be assessed by utilization of the Modified Bromage Scale. Pinprick testing in the mid-clavicular line will be used to check the sensory blockade regression time up to S2 bilaterally. Once the sensory block to S2 and motor block in the lower limbs have fully regressed, evaluations will stop. A >20% drop in systolic blood pressure from the baseline blood pressure, i.e., hypotension, will be treated with IV injection of ephedrine 0.25 to 1 mg/kg or IV fluids or both based on requirements. Atropine 0.6 mg IV injection will be administered to treat bradycardia, which is defined as a drop-in heart rate below 50 beats per minute. Intraoperatively, no analgesia will be given through the intravenous route. Injection diclofenac kept as rescue analgesia if needed. The amount of time (in minutes) from the first instance of urination will be noted; bladder catheterisation will only be carried out if surgically necessary. The need for rescue analgesia will also be noted, and inj. diclofenac 75 mg intramuscularly (i.m.) will be administered on VAS score of 4 post-operatively. The following parameters will be observed and recorded: Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse rate (PR) and percent of haemoglobin saturated with oxygen (SpO₂) will be recorded: baseline values: before (drug administration) and after drug administration at every hour for 24 hours. Loss of sensation to pinprick will be used to establish the upper and lower spread of sensory block, and the Modified Bromage Scale will be used to evaluate motor block.

Post-operative pain analysis

Visual analog scale (VAS)

Patients will receive thorough preoperative instruction. Rescue analgesia will be given at a VAS score of 4 or above in the post-operative ward after the scores have been evaluated using the VAS scale (Table 3).

Block evaluation

Sensory block

Utilising a 27 G needle, the level of sensory block will be assessed, making use of the pinprick method, along the mid clavicular line. The level will be tested from the start of sensory block level reaching T6 level, every two minutes until the maximum sensory block is reached. The period of time from the termination of the injection of anaesthetic agent to the loss of sensation to a pinprick at the T10 level is considered as the onset of sensory blockade (Table 4).

Duration of sensory blockade

The assessment of duration of sensory blockade will be conducted by use of the two segment regression technique. It will involve the measurement of the time period from administration of local anaesthetic agent till the regression of maximum level of sensory blockade by two segments.

The grade of sensory block will be noted (Table 4). The time required for regression of blockade will be noted.

Motor blockade

The quality of motor block will be assessed with the Modified Bromage Scale (Table 5).

Onset of motor blockage: The time period between administration of sub-arachnoid block and development of Bromage level 3 of motor block.

Initiation of surgery will proceed only after establishment of complete anaesthesia.

Following the start of surgery, periodic testing for both motor and sensory levels will be carried out.

In the post-operative period, we will record the time required for regression to level L1 along with the time required for regression from maximum level using two segment regression evaluation.

Post-surgery, pain levels of the subjects will be evaluated for the level of pain by making use of the VAS Scale in the recovery and post-operative room.

Dissemination

The findings of this study will be made available to the scientific community through publication in peer reviewed journals.

Study status

Control group data collection ongoing.

Ethical considerations

The study was approved by the Institutional Ethical Committee, Datta Meghe Institute of Medical Sciences, Sawangi (M), Wardha. Ref. No. DMIMS (DU)/IEC/2022/95.