ISSN(O): 2320-5407 Int. J. Adv. Res.

13(05), May-25, 146-151

Journal Homepage: -www.journalijar.com

Article DOI:10.21474/IJAR01/20887
DOI URL: http://dx.doi.org/10.21474/IJAR01/20887

RESEARCH ARTICLE

PRE-EMPTIVE ANALGESIA WITH PREGABALIN IN ELECTIVE LOWER LIMB

ORTHOPAEDIC SURGERIES: A RANDOMIZED CONTROLLED TRIAL

Satva Thangarasu and Ashish Bangari

……………………………………………………………………………………………………....
Manuscript Info Abstract
……………………. ………………………………………………………………
Manuscript History Background: Postoperative pain in orthopaedic surgeries, particularly
Received: 24 March 2025 lower limb procedures, is severe and can delay rehabilitation. Pre-
Final Accepted: 27 April 2025 emptive analgesia aims to prevent central sensitization by
Published:May 2025 administering analgesics before surgical injury.
Objective: To evaluate the efficacy of pre-emptive pregabalin in
Key words:-
Pre-emptiveanalgesia, pregabalin, reducing postoperative pain and opioid consumption in elective lower
postoperative pain, orthopaedic surgery, limb orthopaedic surgeries.
central sensitization Methods: A randomized, double-blind, placebo-controlled trial
enrolled 60 patients undergoing elective lower limb orthopaedic
surgeries. Patients received pregabalin (150 mg) or placebo one hour
before surgery. Primary outcome was postoperative pain score (Visual
Analog Scale, VAS) at 24 hours; secondary outcomes included opioid
consumption and adverseeffects.
Results:
ThetimetofirstepiduraltopupforPregabalingroupis11.2±5.3hourswhen
compared to 4.67±5.3 hours for control group (p<0.05). The total
number of top upfor pregabalin group is 0.96±0.41 when compared to
control group 1.7±0.7 (p<0.05). The total number of rescue morphine
for pregabalin group is 0.47±0.6 whencompared to control group 1.57
± 0.67 (p< 0.05).
Conclusion: Pre-emptive pregabalin reduces postoperative pain and
opioid requirements in lower limb orthopaedic surgeries, supporting its
use in multimodal analgesia.

"© 2025 by the Author(s). Published by IJAR under CC BY 4.0. Unrestricted use allowed
with credit to the author."
……………………………………………………………………………………………………....
Introduction:-
Postoperative pain following orthopaedic surgeries, particularly lower limb procedures, is often severe, contributing
to delayed rehabilitation, prolonged hospital stays, and increased risk of chronic pain [1]. The International
Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience associated with
actual or potential tissue damage [2]. Surgical tissue injury triggers peripheral and central sensitization, amplifying
pain through heightened responsiveness of nociceptive neurons and reduced pain thresholds [3]. Peripheral
sensitization results from inflammatory mediators lowering the threshold of nociceptors, while central sensitization
enhances dorsal horn neuron excitability, leading to hyperalgesia and allodynia [4].

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Pre-emptive analgesia, administered before surgical incision, aims to block nociceptive input, preventing or
reducing sensitization [5]. Unlike postoperative analgesia, pre-emptive strategies may mitigate the establishment of
pain hypersensitivity, potentially reducing analgesic requirements and improving outcomes [6]. Various agents,
including non-steroidal anti-inflammatory drugs, opioids, and local anaesthetics, have been studied, with mixed
results on efficacy. Pregabalin, a gabapentinoid, binds to the α2δ subunit of voltage-gated calcium channels,
reducing neurotransmitter release and attenuating neuropathic and postoperative pain. Clinical studies suggest
pregabalin decreases postoperative opioid use and preoperative anxiety without significant side effects [7].Given the
high pain burden in lower limb orthopaedic surgeries and the potential of pregabalin to modulate pain pathways, this
study evaluated the efficacy of pre-emptive pregabalin in reducing postoperative pain and opioid consumption
compared to placebo in patients undergoing elective lower limb orthopaedic procedures.

Materials and Methods:

This prospective, randomized, double-blind controlled study was conducted from May 2017 to May 2018 at MIOT
Hospital, Chennai, in accordance with the institutional ethical committee guidelines. Sixty patients scheduled for
elective lower limb orthopaedic surgery, aged 19–60 years and classified as ASA physical status I or II, were
enrolled. Patients undergoing emergency surgery; those with pre-existing neurological, liver, renal, or psychiatric
disorders; local lumbar infections; coagulation disorders; allergies to gabapentinoids; ASA classes III–V; chronic
pain medication users; or those refusing consent were excluded.
Patients were randomly allocated into two groups (n = 30 each) using computer-generated random numbers in a
double-blind fashion. Group P received 300 mg pregabalin, while Group C received a placebo.Sample size
calculation was performed using nMaster 2.0 software and, based on previous study data, indicated that 28 patients
per group were required to achieve 90% power with a 1% type I error. To compensate for an anticipated 10%
attrition rate, 30 patients were enrolled in each group. The calculation was based on the formula for two means with
equal variances:n = [(Zα/2 + Zβ) ² × 2σ²] / d²; where Zα/2 is the critical value for the desired confidence level, Zβ is
the critical value for the desired power, σ² represents the pooled variance, and d is the detectable mean difference.
Preoperative Preparation and Consent
All enrolled patients underwent a comprehensive preoperative evaluation including clinical examination, routine
biochemical tests, electrocardiography, and chest X-ray. Eligible patients, identified per the selection criteria,
received an explanation of the anaesthesia procedure in their vernacular language, and written informed consent was
obtained.
Randomization and Drug Administration Sixty patients scheduled for elective lower limb orthopaedic surgery were
randomized in a double‐blind manner into two groups (n = 30 each) using a computer-generated table. Group P
received a 300 mg capsule of pregabalin (MAXGALIN, Sun Pharma) and Group C received an identical placebo
tablet 90 minutes before anaesthesia. No additional premedication was administered.
Anaesthetic Technique Upon arrival in the operating room, baseline vitals (heart rate, systolic/diastolic blood
pressure, mean arterial pressure, and respiratory rate) were recorded. An 18G IV cannula was placed, and patients
were preloaded with crystalloids (10 ml/kg). Under strict asepsis and with patients in the sitting position, the
epidural space was identified at the L2–L3 or L3–L4 interspace using a 16G Tuohy needle and the loss-of-resistance
technique. An 18G catheter was threaded cephalad (3–4 cm inside) and a test dose (3 cc of 1.5% lignocaine with
adrenaline 5 μg/ml) administered. Spinal anaesthesia was then performed in the same interspace with 3 cc of 0.5%
hyperbaric bupivacaine. Cases exceeding 125 minutes or those requiring intraoperative epidural supplementation
were excluded.
Intraoperative Management
Continuous monitoring was performed every 5 minutes using ECG, NIBP, pulse oximetry, and urine output, with
supplemental oxygen (4–5 L/min via a face mask) and IV midazolam (0.05 mg/kg) for anxiolysis. Motor block was
assessed using the modified Bromage score, and sensory block was evaluated with a spirit swab (at 5 and 10
minutes). Hypotension (>20% drop from baseline) was managed with IV fluids and ephedrine (3 mg increments),
bradycardia (<50 bpm) with IV atropine (0.3 mg), and respiratory depression (RR <8/min) was recorded.
Postoperative Monitoring and Analgesia
Patients were observed in the recovery room for 60 minutes before being transferred to the ward. Postoperative
assessments included continuous monitoring of vitals and evaluation of pain intensity using the visual analogue
scale (VAS) at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, and 24 hours. Sedation levels were recorded using the Ramsay
sedation scale at designated intervals (1, 2, 4, 6, 8, 12, 16, and 24 hours). When VAS reached ≥4, an epidural top-up
(6 ml of 0.125% bupivacaine with 2 μg/ml fentanyl) was administered; persistent pain was treated with rescue IM
morphine (4 mg). All patients additionally received IV paracetamol (1 g thrice daily). Postoperative pain
management was continued with an epidural infusion of 0.125% bupivacaine with fentanyl (2 μg/ml at 4–6 ml/hr),

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and patients were monitored for adverse events, including hypotension, bradycardia, and respiratory depression.
Additional postoperative care included haemoglobin and haematocrit measurement at 24 hours, drain removal after
48 hours, and twice-daily screening for deep vein thrombosis with prophylaxis provided by enoxaparin 40 mg SC
daily until discharge.
Statistical Analysis Continuous data are presented as mean ± SD and categorical data as percentages. Group
comparisons were performed using Student’s t-test for continuous variables and the chi-square test for categorical
variables. A two-tailed p-value <0.05 was considered statistically significant. Data analysis was performed using
SPSS version 17.0.
Results:
In this randomized controlled trial, 60 ASA I–II patients (aged 20–60 years) undergoing elective lower limb
orthopaedic surgery with combined spinal–epidural anaesthesia were randomized to receive pregabalin 300 mg
(Group P, n=30) or placebo (Group C, n=30) 90 minutes preoperatively. Baseline characteristics, including age
(38.17 ± 8.89 vs. 40.10 ± 10.69 years; p=0.45), sex (86.67% vs. 70.00% male; p=0.2092), ASA status (56.7% vs.
70% ASA I; p=0.426), BMI, and surgical duration (105.27 ± 7.86 vs. 104.87 ± 8.02 min; p=0.8460), were
comparable, with no prior surgery at the same site.
Intraoperative parameters, including motor block onset (Bromage score 3) and sensory block levels at 5 and 10
minutes, showed no significant differences (p>0.88). Postoperatively, Group P demonstrated significantly lower
visual analogue scale (VAS) pain scores at most time points (1–24 h; p<0.05), except at 12 h, where Group C had
lower scores (2.1 ± 0.84 vs. 3.2 ± 0.92; p<0.001) due to additional rescue analgesia. Group P required fewer epidural
top-ups (0.96 ± 0.41 vs. 1.7 ± 0.70; p<0.0001) and had a prolonged time to first top-up (11.2 ± 5.3 vs. 4.67 ± 1.9 h;
p<0.001). Rescue morphine use was significantly lower in Group P (0.47 ± 0.62 vs. 1.57 ± 0.67 doses; p<0.0001),
with 60% requiring no morphine compared to 6.7% in Group C.

VisualAnalogueScale-Painscore
3.5
3.2
2.9
3 2.572.432.532.43 2.6 2.67
1.07

2.2

2.1
2.5 1.83 1.87 1.77
1.53 1.6 1.6
1.4

1.5
1.27
1.37
2 0.33
0.23
1.5 0.03
1

0.5

0 CONTROLGROUP PREGABALINGROUP
Mean ± SD

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Figure 1: Pain score comparing control and pregabalin group

FirstEpiduralTopUp (Hour)

100
86.7
80

60
60
40

20

0
16.7 16.7
Number of Patients

13.3
6.7
0 0
Total number of Top up

CONTROLGROUP PREGABALINGROUP
<=5 HOURS 6-10 HOURS 11-15 HOURS 16-24 HOURS

Figure 2: Time to the first epidural top-up in control and pregabalin group

Figure 3: Total number of epidural top-up in control and pregabalin group

TotalnumberofEpiduralTop up
30
25
25
19
20

15 CONTROLGROUP

10 7
PREGABALIN
5 2 3 2 2 GROUP
0
0
0 1 2 3

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These findings indicate that preoperative pregabalin significantly enhances postoperative analgesia, reducing pain
intensity and the need for supplemental analgesics, thus improving patient outcomes in orthopaedic surgery.
Discussion:
Historically, pain management received limited attention until initiatives such as Dr. James Campbell’s 1995
proposal to include pain as a vital sign and the U.S. declaration of the ―Decade of Pain Control and Research‖ in
2000 refocused efforts on effective pain treatment [8]. Despite these efforts, acute postoperative pain after surgical
procedures—especially in orthopaedic cases—remains a significant challenge, with poorly managed pain
contributing to persistent pain syndromes in up to 50% of patients.
Multimodal analgesia, which combines agents like local anaesthetics, opioids, NSAIDs, and other adjuvants, is now
widely employed to harness synergistic effects for better pain control. Among pre-emptive strategies, pregabalin has
gained interest due to its improved pharmacokinetic profile compared to gabapentin. Its enhanced lipid solubility,
rapid absorption (achieving peak plasma concentrations within one hour), and high-affinity binding to calcium
channels contribute to a prolonged pain-free interval following spinal anaesthesia.
Clinical studies corroborate these benefits. For instance, Buvanendran et al. demonstrated that administering
pregabalin (300 mg) preoperatively can reduce postoperative opioid use and improve early rehabilitation outcomes
in total knee replacement patients [9]. Similarly, Jain et al. observed significant reductions in morphine consumption
in patients receiving pregabalin. Studies conducted in the Indian population have also shown that pregabalin not
only prolongs the time to rescue analgesia but may improve overall patient satisfaction without compromising
intraoperative haemodynamics. However, contrasting evidence exists; for example, studies by Mathieson et al. and
Micheal et al [10] did not find significant differences in pain scores or opioid consumption with pregabalin,
underscoring the variability in outcomes across different surgical contexts.
Overall, while pregabalin shows promise as an effective pre-emptive analgesic in orthopaedic surgery, these mixed
findings highlight the need for further research to optimize dosing strategies and integrate it into a comprehensive,
multimodal pain management protocol.
Limitations of the Study:
This study has notable limitations. Pregabalin was administered 1.5 hours preoperatively, consistent with its rapid
absorption (WHO report), but optimal timing for pre-emptive analgesia is unclear, as 2–8 hours may be needed for
effective CSF concentrations (Buvanendran et al.). A 300 mg dose was used, yet doses from 75 mg to 600 mg
require further study for optimization. The additive effects of morphine and pregabalin confounded sedation and
pain control assessments. Range of motion of the traumatized limb was not evaluated. Hospital stay duration was not
compared, despite potential prolongation from pregabalin’s side effects (dizziness, vomiting, blurred vision, and
headache). Patient satisfaction scores were not recorded.

Conclusion
Preoperative administration of pregabalin 300 mg, given 90 minutes before surgery as pre-emptive analgesia,
effectively reduces postoperative pain scores and significantly decreases the need for postoperative analgesics in
lower limb orthopaedic surgeries, with no major adverse effects observed.

Results:

Pregabalin Control p
group group value
Timetofirstepiduraltopup 11.2±5.3 4.67±1.9 <0.001
Totalnumberofepiduraltop-up 0.96±0.41 1.7±0.7 <0.001
Meanrescue Morphine 0.47±0.6 1.57±0.6 <0.001

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