This study proposes to compare current multimodal analgesic treatment for TKA with a new multimodal analgesic regimen to demonstrate decreased opioid requirement, time to rehabilitation, and time to reach hospital discharge.

Total knee replacement surgery (TKA) causes severe pain and this procedure is the most common reason patients are prescribed strong opioid drugs in hospital. As a result they are slow to begin rehabilitation after surgery, and are late in hospital discharge. Ontario hospitals are constantly challenged to meet growing demands of TKA and in fact increased demand has overcome the health care system resulting in TKA wait time (Ontario actual: 286 days vs. target: 182 days).1 One strategy to accommodate expanding volume and reduce wait time is to reduce hospital length of stay (LOS) through an enhanced recovery program.2 One essential component is further improvement of postoperative pain treatment to expedite rehabilitation and hospital discharge.

Treatment of severe post TKA pain often requires potent opioids but their excessive and prolonged use has negative consequences e.g., increased perioperative adverse events and longer LOS.3 Approximately 8% of opioid naive TKA patients become chronic opioid users at 6 months and the duration of prescription is the strongest predictor of misuse.4 Knowing that the opioid crisis in Canada is steadily growing and prescription opioids play a significant role in dependence and misuse,5 an effective perioperative opioid minimization analgesic program is mandatory for TKA patients.

Current multimodal analgesic treatment for TKA consists of oral non opioid drugs e.g., acetaminophen and non steroidal anti-inflammatory agents (NSAIDs) and surgeon performed peri-articular local anesthesia infiltration, however this is only partially effective.6 The regional analgesic effect is often short lived (< 8 hours). Failure to sustain effective analgesia necessitates continued heavy reliance on opioids.

Several new treatments have been recently described for post TKA pain. They are: IV dexamethasone (steroid),7 dexmedetomidine (alpha 2 agonist)8, ketamine (NMDA antagonist)9 and 2 novel nerve block procedures- adductor canal block10 and iPACK block (infiltration between popliteal artery and posterior capsule of the knee).11 While each individual intervention has demonstrable analgesic benefit, the impact of incorporating all new treatments into the current analgesic regimen remains unknown.

The investigators believe that the new multimodal analgesic regimen proposed in this study will significantly decrease opioid requirement, time to rehabilitation, and time to reach hospital discharge criteria. It may also decrease the duration of opioid prescription for pain relief after hospital discharge. Although investigator's preliminary experience with this new regimen in 10 patients is promising, robust evidence showing its sustained opioid sparing analgesic effect is lacking.

Inclusion criteria:

• English-speaking;
• Age 18 - 85;
• BMI ≤ 38;
• Undergoing unilateral primary total knee arthroplasty surgery.

Exclusion criteria:

• inability to give informed consent
• patient refusal
• pregnancy, patients who are breastfeeding
• contraindication to nerve blocks or multimodal analgesia
• contraindication or hypersensitivity to any of the study drugs (celecoxib, acetaminophen, morphine, ropivacaine, bupivacaine, ketamine, dexmedetomidine, dexamethasone, ketorolac, epinephrine, sulfonamides)
• chronic pain disorders (> 50 mg oral morphine equivalence per day at time of recruitment)
• medical or recreational use of marijuana and substance abuse (e.g., alcoholism),
• complications after surgery that result in discharge to a location other than home
• severe cardiovascular diseases e.g., heart failure, significant dysrhythmias; uncontrolled low blood pressure e.g., systolic blood pressure ≤ 100 mm Hg while on antihypertensive medication(s)
• respiratory diseases e.g., severe asthma, urticaria, or allergic-type reactions after taking acetylsalicylic acid (ASA) or other NSAIDs; severe acute or chronic respiratory disease and obstructive airway
• severe or active liver disease
• severe inflammatory bowel disease
• severe renal impairment (creatinine clearance <30 mL/min)
• uncontrolled diabetes (type 1 or 2)
• active bleeding condition (e.g., postoperative or gastro-intestinal bleeding)
• severe psychiatric disorders and intake of monoamine oxidase inhibitors
• neurologic disorders (e.g., operative extremity neuropathy, delirium tremens, uncontrolled convulsive disorders, increased cerebrospinal or intracranial pressure)

Block room and anesthesia staff performing nerve blocks and administering sedation will be informed to which study group patient is allocated. The patient and independent investigator carrying out follow up assessments will remain blinded to the end of the study. If the patient wishes to know the study group assignment, the patient will be informed at the end of their final 6 week follow up.