What is the role of celecoxib (celecoxib) and pregabalin (pregabalin) in preoperative management of total knee replacement (TKR) patients?

Preoperative Celecoxib and Pregabalin for Total Knee Replacement

Celecoxib should be used routinely in the perioperative period for TKR patients, while pregabalin should NOT be used routinely due to clinically significant side effects that outweigh its benefits.

Celecoxib Recommendation

Celecoxib is strongly recommended as part of basic analgesia for TKR patients unless contraindicated. 1

Dosing Protocol

• Preoperative: 400 mg administered 1-2 hours before surgery 2
• Postoperative: 200 mg every 12 hours for 5-10 days 2, 3
• Alternative regimen: 100 mg twice daily starting 7 days preoperatively, then 200 mg every 12 hours postoperatively 2

Evidence Supporting Celecoxib Use

• Pain reduction: Significantly lower pain scores at 48 hours (2.13 vs 3.43, p=0.03) and 72 hours (1.78 vs 3.17, p=0.02) compared to placebo 3
• Opioid-sparing effect: Reduces opioid consumption by approximately 40% (p=0.03) 3
• Functional outcomes: Greater active range of motion in first 3 days postoperatively (77.7° vs 64.3° on day 3, p=0.004) 3
• Long-term benefits: Better Knee Society Score at 12 months (93.3 vs 86.4, p<0.001) 2
• Earlier mobilization: Faster achievement of 90° knee flexion (p<0.001) 2
• Reduced side effects: Lower incidence of nausea, vomiting, and pruritus compared to opioid-only regimens 2

Safety Profile

• No increased bleeding risk: Celecoxib does not increase perioperative blood loss or transfusion requirements 3, 4
• No need to discontinue preoperatively: Can be safely continued through surgery 4

Pregabalin Recommendation

Pregabalin is NOT recommended for routine use in TKR patients due to clinically relevant side effects, despite some evidence of pain reduction. 1

Evidence Against Routine Pregabalin Use

The PROSPECT guidelines (2021) explicitly state that "repeated doses of peri-operative gabapentinoids show evidence of pain reduction but are not recommended as routine medication due to clinically relevant side-effects." 1

Side Effects Outweigh Benefits

• Sedation: Significantly increased on day of surgery and postoperative day 1 (p=0.005) 5
• Confusion: More frequent in pregabalin patients (p=0.013) 5
• Dizziness: Consistently reported across multiple studies 1
• No morphine-sparing effect: When combined with celecoxib for 2 weeks pre-op and 3 weeks post-op, morphine consumption did not differ despite more side effects 1

Mixed Evidence on Efficacy

• Inconsistent pain reduction: Meta-analyses found morphine-sparing effects but were inconsistent regarding actual pain reduction 1
• Context-dependent benefit: Pregabalin 150 mg showed effectiveness only when added to a basic analgesic regimen already containing celecoxib and morphine PCA 1
• Chronic pain prevention: While one study showed reduced neuropathic pain at 3 and 6 months (0% vs 8.7% and 5.2%, p=0.001 and p=0.014), this benefit came with significant early cognitive side effects 5

When Pregabalin Might Be Considered (Not Routine)

If pregabalin is used despite guideline recommendations against routine use, the dosing would be:

• Preoperative: 150 mg administered before surgery 1
• Postoperative: 75-150 mg twice daily for up to 14 days 5
• Maximum dose: 300 mg/day in divided doses 6

Critical caveat: This should only be considered in highly selected patients with pre-existing neuropathic pain conditions, not as routine practice for all TKR patients. 1

Combined Celecoxib-Pregabalin Regimen

The combination of celecoxib and pregabalin is NOT recommended for routine use. 1

• When studied as a 2-week preoperative and 3-week postoperative regimen (celecoxib + pregabalin 75 mg twice daily), patients experienced less acute pain on postoperative day 1, but morphine consumption did not differ and there were MORE side effects in the combination group 1
• A single-dose preemptive combination (celecoxib 400 mg + pregabalin 150 mg) reduced morphine use but showed no advantage over repetitive dosing and did not improve range of motion or mobilization 7

Practical Algorithm for TKR Pain Management

Standard Approach (All Patients)

1. Celecoxib: 400 mg 1-2 hours preoperatively, then 200 mg every 12 hours for 5-10 days 2, 3
2. Regional anesthesia: Spinal or epidural preferred over general anesthesia 1
3. Dexamethasone: 10 mg perioperatively (reduces pain scores >20 mm, reduces opioid consumption, shorter hospital stay) 1
4. Opioid PCA: As needed for breakthrough pain 2, 3

Avoid Routine Use

• Pregabalin: Do not use routinely due to sedation, confusion, and dizziness without consistent pain reduction benefit 1
• Gabapentin: No analgesic benefit when used as sole intervention 1

Special Populations

• Diabetic patients: Monitor glucose if using dexamethasone (small but significant increase in blood glucose) 1
• Patients with contraindications to celecoxib: Consider alternative NSAIDs, though no specific NSAID has proven superiority 1