2.3. Design and Conduct of the Study
postoperative nausea and vomiting, pain, dizziness, PONV, urinary retention
INFILTRATION, DEEP VEIN THROMBOSIS (DVT), ADVERSE EFFECTS, GASTROINTESTINAL HEMORRHAGE, COMPLICATIONS
Pregabalin and celecoxib are produced by Pfizer in the United States under the trade names Lyrica and Celebrex, respectively. Pregabalin, celecoxib, and the placebo were packaged in the same opaque packaging by the University Hospital Health Research Center pharmacy. The placebo capsule contained a mixture of 50% cellulose and 50% starch. An assistant from the Clinical Research Center used a random number table to divide the patients into four groups: the control group, celecoxib group, pregabalin group, and combination group. The patient group assignments were sealed in envelopes. Anesthesiologists who did not participate in the study opened the envelope 12 hours before the surgery, distributed drugs according to the patient group assignment, and distributed the same drugs again 2 hours before the surgery. The researchers involved did not know the patient group assignment during the surgery or data analysis. The medication program was as follows: placebo group: 200 mg + 150 mg placebo; pregabalin group: 150 mg pregabalin + 200 mg placebo; celecoxib group: 200 mg celecoxib + 150 mg placebo; and pregabalin combined with celecoxib group: 150 mg pregabalin + 200 mg celecoxib. Each group was given the same medication program again 2 hours before surgery. The patients were closely monitored for adverse effects after each administration of the medicine. All patients were given general anesthesia by senior anesthesiologists in our hospital. All operations were performed by two senior doctors with more than ten years of experience in TKA. Periarticular infiltration of the cocktail ingredient (0.5% ropivacaine + 10 mg/ml triamcinolone acetonide acetate + 0.1% epinephrine hydrochloride) was performed before closed the incision. Afterwards, the four groups of patients received patient-controlled intravenous analgesia (PCIA) immediately after the laryngeal mask was removed. The analgesic formula was sufentanil 2 The main observation indicators included the following:(1) VAS pain score at rest and upon movement at 6, 12, 24, and 48 hours after the surgery (from 0: no pain to 10: worst possible pain; pain upon movement was pain upon maximum flexion of the knee); (2) cumulative dose of opioids within 48 hours (including total sufentanil and morphine remedial analgesic dosages, all converted to sufentanil equivalent); (3) the hs-CRP level before and after the surgery; (4) time of first successful straight leg elevation: the standard is that the patient can maintain a flexed ankle joint and straight leg raise at least 40 cm above the bed for more than 4 s; (5) maximum knee flexion range of motion (ROM) at 24, 48, and 72 hours after surgery; (6) time to first remedial analgesia after surgery; and (7) complications including postoperative nausea and vomiting (PONV), dizziness, gastrointestinal hemorrhage, urinary retention, deep vein thrombosis (DVT), and severity of sedation.