Acute Postoperative Pain, Lower Limb Surgery
Conditions
Keywords
Tapentadol, Pregabalin, Preemptive analgesia, Acute postoperative pain, Lower limb surgery, Neuraxial anesthesia, Pilot randomized controlled trial
Brief summary
This pilot randomised controlled trial compared 72-hour oral premedication with tapentadol (50 mg every 12 hours) versus pregabalin (75 mg every 24 hours) for preventing acute postoperative pain in 46 patients undergoing elective lower limb surgery under neuraxial anaesthesia. The primary outcome was pain intensity measured by the Numeric Rating Scale (NRS 0-10) at PACU arrival and at 30, 60, 90, and 120 minutes thereafter. Secondary outcomes included Verbal Rating Scale scores, rescue morphine consumption, and safety (nausea/vomiting, hypersensitivity).
Detailed description
Acute postoperative pain affects over 80% of surgical patients, with orthopaedic lower limb procedures causing particularly severe pain. Preemptive analgesia may attenuate central sensitisation before surgical incision. Tapentadol (μ-opioid agonist + norepinephrine reuptake inhibitor) and pregabalin (voltage-gated calcium channel modulator) are pharmacologically distinct options, but direct comparative data are lacking. This single-centre, double-blind, parallel-group pilot randomised controlled trial was conducted at Hospital Regional "General Ignacio Zaragoza," ISSSTE, Mexico City. Forty-six patients (ASA I-II, age 18-50 years, BMI 18-35 kg/m²) scheduled for elective lower limb surgery under neuraxial anaesthesia were randomised 1:1 to receive either tapentadol 50 mg orally every 12 hours (n=23) or pregabalin 75 mg orally every 24 hours (n=23), both initiated 72 hours before surgical incision. The primary outcome was postoperative pain intensity assessed using the Numeric Rating Scale (NRS 0-10) at PACU arrival (T0) and at 30 (T1), 60 (T2), 90 (T3), and 120 (T4) minutes thereafter. Secondary outcomes included Verbal Rating Scale (VRS) scores, rescue morphine consumption (4 mg IV on request), and incidence of nausea/vomiting and hypersensitivity reactions. The primary longitudinal analysis used a linear mixed model with Group, Time, and Group×Time interaction as fixed effects and a random intercept per patient. Between-group contrasts at each timepoint were derived from estimated marginal means with Holm correction. Effect sizes are reported as Cohen's d. The trial was approved by the institutional ethics and research committee (RPI #386-2024) and registered with the ISSSTE institutional research registry prior to enrolment. Due to institutional policy restrictions at the time of study initiation, registration on ClinicalTrials.gov was completed after data collection; this is disclosed transparently in accordance with CONSORT 2025 guidance on retrospective registration disclosure.
Interventions
DRUGTapentadol
Tapentadol 50 mg immediate-release oral tablet administered every 12 hours for 72 hours preoperatively (total of 6 doses).
DRUGPregabalin
Pregabalin 75 mg oral capsule administered every 24 hours for 72 hours preoperatively (total of 3 doses).
Sponsors
ISSSTE Hospital Regional "Gral. Ignacio Zaragoza"
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind trial. Study drugs were prepared and dispensed in identical oral formulations by personnel not involved in patient care or outcome assessment. Neither patients nor the treating anaesthesiologist nor the outcome assessor knew group assignment throughout the study period.
Intervention model description
Two-arm parallel-group pilot RCT. Participants were randomised equally (n=23 per group) to receive 72-hour oral premedication with tapentadol (50 mg q12h) or pregabalin (75 mg q24h).
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-50 years * ASA physical status I or II * Body mass index between 18 and 35 kg/m² * Scheduled for elective lower limb surgery under neuraxial anaesthesia * Willing to provide written informed consent
Exclusion criteria
* Chronic use of analgesics or gabapentinoids * Known hypersensitivity to tapentadol or pregabalin * Pre-existing chronic pain Elimination Criteria: * Hypersensitivity reaction to any study drug during administration * Hemodynamic shock of any etiology * Requirement for advanced airway management or postoperative mechanical ventilation * Surgical duration exceeding 120 minutes * Requirement of an epidural catheter dose within the first two postoperative hours * Voluntary withdrawal of consent at any point
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain intensity by Numeric Rating Scale (NRS) | At PACU arrival (T0), 30 minutes (T1), 60 minutes (T2), 90 minutes (T3), and 120 minutes (T4) post-arrival | Postoperative pain intensity measured using the Numeric Rating Scale (NRS, 0-10; 0 = no pain, 10 = worst imaginable pain). The primary longitudinal analysis used a linear mixed model with Group, Time, and Group×Time interaction as fixed effects and a random intercept per patient. Between-group contrasts at each timepoint were derived from estimated marginal means with Holm correction. Effect sizes reported as Cohen's d. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Verbal Rating Scale (VRS) pain category | At PACU arrival (T0), 30 minutes (T1), 60 minutes (T2), 90 minutes (T3), and 120 minutes (T4) post-arrival | Pain severity categorised as absence, low, moderate, or severe using the Verbal Rating Scale (VRS). Reported as proportions of patients in each category at each timepoint. |
| Rescue morphine consumption | During the two-hour PACU observation period (T0-T4) | Proportion of patients requiring rescue analgesia (morphine 4 mg IV) and total morphine consumption (mg) in each group. |
| Incidence of nausea and vomiting | During the two-hour PACU observation period (T0-T4) | Proportion of patients experiencing nausea and/or vomiting in each group, assessed by clinical observation and patient report. |
| Hypersensitivity reactions | From first dose of study medication through 24 hours post-surgery | Incidence of any hypersensitivity or anaphylactic reaction to tapentadol or pregabalin, classified according to Müller criteria. |
Countries
Mexico
Outcome results
None listed