What medications should be used with ketamine (Ketamine) for a total knee replacement (TKR)?

Ketamine for Total Knee Replacement: Multimodal Analgesic Protocol

Ketamine should be used as part of a multimodal analgesic regimen that includes regional anesthesia (femoral nerve block or adductor canal block), scheduled paracetamol, NSAIDs or COX-2 inhibitors, and opioids for breakthrough pain. 1

Primary Anesthetic and Regional Technique

Start with general anesthesia combined with femoral nerve block (or adductor canal block), or alternatively use spinal anesthesia with local anesthetic plus spinal morphine. 1, 2 The evidence strongly supports femoral nerve block as the primary regional technique, demonstrating reduced pain scores and supplemental analgesic requirements. 1

Ketamine Administration Protocol

Intravenous Ketamine Dosing

For perioperative IV ketamine, administer an initial bolus of 0.5 mg/kg followed by continuous infusion of 3 μg/kg/min during surgery, then reduce to 1.5 μg/kg/min for 48 hours postoperatively. 3 This regimen has demonstrated:

• Significant reduction in morphine consumption (45 mg vs 69 mg over 48 hours) 3
• Decreased opioid use in the first 24 hours after surgery 1
• Faster achievement of 90° active knee flexion (7 days vs 12 days) 3
• Lower pain scores at 6,12,24, and 48 hours postoperatively 4

Alternative low-dose regimen: 6 μg/kg/min continuous infusion intraoperatively has also shown efficacy in reducing postoperative pain and morphine consumption. 5

Intra-articular Ketamine

Intra-articular ketamine is NOT recommended due to inconsistent analgesic efficacy in procedure-specific evidence. 1 Studies of intra-articular S(+)-ketamine showed no statistical superiority over saline solution. 6

Epidural Ketamine

Epidural ketamine as an adjunct to local anesthetics and opioids shows inconclusive results and cannot be recommended based on current evidence. 1

Essential Multimodal Components to Combine with Ketamine

Scheduled Non-Opioid Analgesics

• Paracetamol (acetaminophen): Administer scheduled doses to reduce supplemental analgesic use 1, 2
• COX-2 selective inhibitors: Superior to placebo for decreasing pain scores up to 3 days post-surgery with reduced supplemental analgesic use 1
• Conventional NSAIDs: Effective alternative if COX-2 inhibitors contraindicated 1

Opioids for Breakthrough Pain

• Strong opioids (IV morphine via PCA): For high-intensity pain, combined with non-opioid analgesia 1
• Weak opioids: For moderate to low-intensity pain if non-opioid analgesia insufficient 1

Non-Pharmacological Adjuncts

Add cooling and compression techniques (Cryo/Cuff) which have shown superiority over standard care for pain reduction. 1, 2

Safety Profile and Side Effects

Ketamine demonstrates an excellent safety profile at these doses with no increased incidence of:

• Sedation, hallucinations, nightmares, or diplopia 3
• Dizziness, sweating, pruritus, urinary retention, or delirium 4

Notably, ketamine may actually reduce postoperative nausea and vomiting compared to control groups. 4

Critical Pitfalls to Avoid

• Do NOT use ketamine as monotherapy - it must be part of multimodal analgesia 1
• Avoid epidural analgesia due to increased risk of serious adverse events without superior benefits 1, 2
• Do NOT combine femoral and sciatic nerve blocks - limited and inconsistent evidence supports this over femoral block alone with systemic analgesia 1
• Avoid intra-articular ketamine administration - inconsistent efficacy 1, 6

Timing Considerations

Initiate ketamine administration before surgical incision to ensure adequate analgesic effect in the immediate postoperative period, continuing the infusion for 48 hours. 3, 7 This timing optimizes both pain control and early rehabilitation outcomes.