Reducing Postoperative Side Effect of Pregabalin
Condition: Pain, Postoperative; Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Hip
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study was to determine 1) if pregabalin, when given 37.5 mg twice on the
      day before surgery, would be effective in reducing the early postoperative side effects
      including dizziness, nausea, vomiting and sedation of receiving pregabalin 75mg two hours
      pre-operatively and 75mg per day until the third postoperative day; and 2) whether this
      intervention affected the opioids consumption, and independent transfers at six hours
      post-op, time to readiness for independent transfers, time to readiness for discharge and
      pain or not.
    

Detailed description: 
      Study design This prospective randomized controlled clinical trial was conducted at our
      institution in accordance with the Declaration of Helsinki. The Institutional Review Board
      approved the study (IRB number IRB00008484). We registered the clinical trial on The
      ClinicalTrials.gov Protocol Registration (NCT04599894) before the enrolment of the first
      participant. Written informed consent was obtained from each patient.

      Participant recruitment Patients were eligible for inclusion if they were between 18 and 80
      years of age and scheduled for a primary TJA. Exclusion criteria included: medical history of
      neuropathic pain or other non-arthritic chronic pain; Non-steroidal anti-inflammatory drug
      intolerance or long-term use of opioids; psychiatric disorders; motion sickness.

      Sample size estimation The sample size was based on a preliminary study (under the same
      synergy of medications, celecoxib (Pfizer) 400mg and pregabalin (Pfizer) 75mg two hours
      pre-operatively orally, on the day of surgery). The preliminary study demonstrated that only
      one patient fell dizziness postoperatively in ten consecutive TJA patients who received
      37.5mg pregabalin twice on the day before surgery, while four patient fell dizziness
      postoperatively in ten consecutive TJA patients receiving none on the day before surgery.
      Therefore the sample size was calculated by comparing estimated proportion using the
      Chi-squared statistic, a sample size of 58 (29 per group) would reveal differences at the 5%
      level of significance, and with a power of 0.8.

      Randomization A computer-generated randomization schedule was used to assign patients to one
      of two treatment groups. The schedule was created by the clinical research center of our
      hospital, which was not involved in the clinical care of patients or in the conduct of the
      present trial.

      Treatment protocol All patients scheduled to undergo primary TJA between November 2020 and
      April 2021 were screened for recruitment. Participants were recruited at their preoperative
      assessment visit two days before surgery and were randomly assigned to one of two treatment
      groups. Group 1 (G1) received pregabalin 37.5 mg twice orally (PO) on the day before surgery
      (at 8 am and 6 pm, respectively), and celecoxib 400mg as well as pregabalin 75mg PO at two
      hours pre-operatively; Group 2 (G2) received none on the day before surgery and the same dose
      of celecoxib and pregabalin PO at two hours pre-operatively. Crystalloid for resuscitation
      was started on the morning of surgery. Perioperative antibiotics, cefazolin sodium, 2g, and
      tranexamic acid 1g were administered within one hour of skin incision via intravenous (IV)
      drip. Dolasetron 12.5mg IV and dexamethasone 5mg IV were administrated during the induction
      of anesthesia. Patients were sedated with midazolam and received a general anesthesia
      combined with fascia iliaca compartment block (FICB) for THA(0.2% ropivacaine 60mg for each
      joint) and adductor canal as well as infiltration between the popliteal Artery and Capsule of
      the Knee (iPACK) block for TKA (totally 0.2% ropivacaine 60mg for each joint). All procedures
      were performed by one group of surgeons (QX, GYH, ZXY, ZJT) through a posterolateral approach
      for THA and medial parapatellar approach for TKA. Periarticular injection (0.2% ropivacaine
      80mg, compound betamethasone 7mg, ketorolac 30mg, epinephrine 0.3mg for each joint) was
      performed before implanting prosthesis. Cementless prosthesis (Depuy, Corail® Total Hip
      System) was used in all hips, and cemented prosthesis (Depuy, Attune® Total Knee System) was
      used in all knees. Neither drain was used in all wounds, nor was urinary catheter. IV
      patient-controlled analgesia (PCA) was not administered in these participants. Since two
      hours after extubation under general anesthesia, participants were allowed to drink water and
      progressively transit to their daily diaries. They were instructed to make independent
      postoperative transfers at six hours after extubation, which was taken as the final time
      point to determine the success of EARS pathway. Then these patients were transferred to a
      rehabilitation unit in the same hospital, cryotherapy and rehabilitation protocols were
      ordered until discharge. Rivaroxaban (10mg at 8 am per day, Bayer), celecoxib (200mg twice a
      day, at 8 am and 2 pm, respectively) as well as pregabalin (75mg per day at 6 pm) until the
      third postoperative day. Patients were instructed to maintain a VAS (visual analogous scale)
      pain score of between 1 and 3. If the VAS pain score was ≥4 at rest, oxycodone-acetaminophen
      (5mg/325mg, per dose, Mallinckrodt Inc.) would be used every six hours as needed for
      postoperative rescue analgesia. The discharge criteria included: patients' general well-being
      and acceptable pain control (VAS<4); dry wound; ability to safely mobilize with crutches and
      climb the stairs; patients' express acceptance of discharge; patients and family members
      learned the home-based exercise protocols for the first six weeks. Rivaroxaban was continued
      to use for five weeks. Cryotherapy, rehabilitation protocols and celecoxib 200mg twice a day
      were continued to use for six weeks postoperatively.
    

Intervention name(s): 37.5mg Pregabalin + 75mg Pregabalin; 75mg Pregabalin
Intervention type(s): Drug; Drug
Intervention description(s): 37.5mg pregabalin preoperatively + 75mg pregabalin postoperatively; 75mg pregabalin postoperatively
Intervention MeSH terms: Pregabalin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: pregabalin; total joint arthroplasty; side effect