Pregabalin, Celecoxib, Total Knee Arthroplasty and Intrathecal Morphine (PCTKA)

Comparison of Analgesic Efficacy Among Pregabalin, Celecoxib, Pregabalin With Celecoxib and Placebo After Total Knee Arthroplasty Under Intrathecal Morphine

To evaluate whether pregabalin and/or celecoxib could improve analgesic efficacy of intrathecal morphine for patients after total knee arthroplasty.

A single-dose spinal anesthesia combining with morphine for total knee arthroplasty (TKA) is a simple, economical anesthetic technique commonly used in our hospital. Still some patients could not get effective postoperative pain control. Pregabalin, an anticonvulsant, has been shown to reduce acute pain after molar extraction, laparoscopic cholecystectomy, and reduce postoperative morphine requirement after total hip arthroplasty, and celecoxib, a selective cyclo-oxygenase (COX) - 2 inhibitor, with perioperative prescription is successfully reduces pain score and opioid consumption after TKA under spinal anesthesia alone. However, no clinical study has yet investigated whether preoperative single-dose of pregabalin, celecoxib or in combination compared to placebo can improve analgesic efficacy of intrathecal morphine after TKA. The primary objective of this study was to evaluate whether these medications could reduce pain scores at rest / when movement and morphine requirement after TKA under spinal anesthesia with intrathecal morphine. Secondary outcome assessed include adverse effects, anxiety score and patients' satisfaction score.

Oral single-dose of pregabalin (150 mg) and 1 capsule of placebo (P) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.

Oral single-dose of celecoxib (400 mg) and 1 capsule of placebo (C) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.

Oral single-dose of pregabalin (150 mg) and celecoxib (400 mg) (PC) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.

Oral single-dose of placebo 2 capsules 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg

Oral single-dose of pregabalin (150 mg) and placebo (P) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.

Oral single-dose of celecoxib (400 mg) and placebo(C)1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.

Oral single-dose of pregabalin (150 mg) and celecoxib (400 mg) (PC) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.

Oral single dose of placebo 2 capsules 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg

The time to first morphine requirement will be recorded The cumulative morphine consumption will be recorded at the end of surgery and 2-h, 6-h, 10-h, 24-h, and 48-h postoperatively Visual analog scale (VAS) pain scores at rest will be assessed at the night before surgical date, before starting anesthesia, at the end of surgery, and 2-h, 6-h, 10-h, 24-h and 48-h postoperatively Visual analog scale (VAS) pain scores when on movement will be assessed at the end of surgery, and 2-h, 6-h, 10-h, 24-h and 48-h postoperatively

Anxiety scores will be assessed at the night before surgical date, before starting anesthesia, at the end of surgery, and 2-h, 6-h, 10-h, 24-h and 48-h postoperatively; 24-h and 48-h patients' satisfaction (0-10,0=dissatisfied and 10= very satisfied)

Inclusion Criteria: Patients between 50-75 years of age Patients with an American Society of Anesthesiologists physical status of I to III Patients scheduled for primary TKA with a diagnosis of osteoarthritis under spinal anesthesia Exclusion Criteria:. Patients had a known allergy to any of the medications being used a history of drug or alcohol abuse a history of taking chronic pain medications (ie, show-release preparations of opioids, given that morphine consumption was the primary outcome) a history of taking pregabalin or gabapentin / non-steroidal anti-inflammatory drugs / COX-2 inhibitors a psychiatric disorder a history of impaired renal function (Cr > 1.5 mg/dl), peptic ulcer, asthma, thrombotic cerebrocardiovascular diseases, uncontrolled hypertension a history of contraindication for spinal anesthesia a history of bleeding tendency pregnancy unable or unwilling to use patient - controlled analgesic (PCA)