Perioperative Cocktail for Total Knee Replacement
The recommended perioperative cocktail for TKR consists of local periarticular injection of a multimodal analgesic mixture containing local anesthetic, opioid, corticosteroid, and NSAID, administered intraoperatively into the periarticular tissues, with subperiosteal injection being superior to traditional periarticular injection for pain and blood loss reduction. 1
Cocktail Composition and Administration
Optimal Injection Technique
- Subperiosteal injection under the periosteum of the distal femur and proximal tibia provides superior outcomes compared to traditional periarticular injection into muscles, tendons, and bursae. 1
- This technique targets the abundant nerves and blood vessels in the periosteum and bone marrow, resulting in significantly lower pain scores (VAS 0.86 vs 0.98 at rest, and 1.10 vs 1.61 with movement on postoperative day 1) and reduced blood loss (333.67 ml vs 440.19 ml on day 1). 1
Clinical Outcomes
- Periarticular cocktail injection significantly reduces early postoperative pain during the first 48 hours and accelerates achievement of 90° knee flexion compared to no injection. 2
- Patients receiving periarticular multimodal drug cocktails demonstrate lower VAS scores on the day of surgery and postoperative day 1, with reduced requirements for supplemental analgesia (diclofenac sodium suppositories). 3
- No cardiac or central nervous system toxicity has been observed with this approach. 3
Antibiotic Prophylaxis Component
Cefazolin Administration
- Administer 1 gram IV cefazolin 30-60 minutes prior to surgical incision to ensure adequate antibiotic levels are present in serum and tissues at the time of initial incision. 4
- For lengthy procedures (≥2 hours), give 500 mg to 1 gram IV cefazolin intraoperatively, with timing modified based on procedure duration. 4
- In prosthetic arthroplasty where infection may be particularly devastating, continue prophylactic cefazolin 500 mg to 1 gram IV every 6-8 hours for 3-5 days postoperatively. 4
Special Considerations for Rheumatic Disease Patients
DMARD Management
- Continue methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine at current doses throughout the perioperative period. 5
- Continuing DMARDs reduces infection risk (RR 0.39,95% CI 0.17-0.91) and decreases disease flares postoperatively (RR 0.06,95% CI 0.0-1.10). 5, 6
Biologic Agent Management
- Withhold all biologic agents prior to surgery and schedule the procedure at the end of the dosing cycle for the specific medication. 5, 7
- Resume biologic agents only after wound healing is confirmed (minimum 14 days) and absence of both surgical site and systemic infection is established. 7, 6
Glucocorticoid Management
- Continue the patient's current daily glucocorticoid dose rather than using "stress-dose" protocols. 5, 6
- Optimal preoperative glucocorticoid dosing should be <20 mg/day prednisone equivalent when possible, as doses >15 mg/day increase infection risk. 5
- No significant hemodynamic benefit exists for stress-dose steroids, and escalating doses increase complication risk. 5, 6
Common Pitfalls to Avoid
- Do not withhold non-biologic DMARDs perioperatively, as this increases both infection and flare risk. 6
- Do not restart biologic agents before confirming adequate wound healing (minimum 14 days) and ruling out infection. 7, 6
- Avoid traditional periarticular injection into superficial tissues only; subperiosteal injection provides superior pain control and hemostasis. 1
- Do not delay preoperative antibiotic administration; cefazolin must be given 30-60 minutes before incision for optimal tissue levels. 4