Study to Examine Pain Relief With Supplemental Intrathecal Morphine in TKA Patients

This is a prospective, case-controlled randomized, double-blinded, placebo-controlled study
expected to enroll up to 100 patients scheduled to undergo unilateral total knee arthroplasty
(TKA) under regional anesthesia (defined as intrathecal spinal + femoral nerve blockade +
femoral nerve catheter for post-operative analgesia) at Stony Brook Hospital. The patients
were randomized to receive either IT morphine 0.2 mg (Group 1) or placebo (Group 2) in
combination with their standard-of-care spinal anesthesia. Post-operatively, the patients
were given an intravenous patient-controlled analgesic opioid for breakthrough pain.

Only the pharmacist preparing the drug/placebo has knowledge of how each subject was
randomized. Study staff completed multiple questionnaires regarding subjects' pain scores and
patient disability from pain to assess changes between different study periods (ie.
pre-operative, post-operative and follow up). Biological samples were also taken from each
subject to measure and analyze differences and changes in endocannabinoid levels.

Inclusion Criteria:

- Scheduled for unilateral TKA under regional anesthesia

- ASA Class 1, 2 or 3

- Able to give informed consent

- Able to understand English

Exclusion Criteria:

- Medical condition(s) that prevents use of regional anesthesia (e.g. infection at site
of injection, coagulopathy, severe hypovolemia, severe aortic or mitral stenosis,
increased intracranial pressure, severe spinal deformity, spinal cord hardware or
stimulator implanted)

- Allergy to morphine

- Morbid obesity (BMI > 45)

- Respiratory compromise (difficult airway, severe emphysema or COPD)

- Obstructive sleep apnea (only if diagnosed in a sleep disorders clinic and CPAP was
prescribed)

- Chronic pain with opioid usage over 100 mg morphine-equivalents po/day

- History of abuse of opioids or other drugs of abuse

- Scheduled for bilateral TKA

- Revision of knee arthroplasty

- Any medical condition that would affect the patient's ability to metabolize or excrete
the study drugs (e.g. chronic kidney failure with patient on dialysis) or other
medical condition that in the investigator's opinion would render the patient
unsuitable for this research study