comparison of the Effectiveness of pre-operative intravenous ketamine administration with placebo in controlling post-operative pain in patients with advanced knee osteoarthritis undergoing total knee arthroplasty

the purpose of this study is to evaluate the safety an efficacy of ketamine to reduce post total knee arthroplasty pain

this is a prospective triple blind single center comparative 2 arm RCT to compare the effectiveness of on bolus dose of intravenous ketamine on post -operative pain after total knee arthroplasty. 60 patients are equally and randomly assigned to group A (ketamine) or group B (PLACEBO/normal saline)

The study will be run in Shariati hospital. Tehran university of medical sciences. After spinal anesthesia single bolus dose of ketamine or placebo is intravenously injected the patients. anesthesiologist, surgeons, data collectors and statistician are blinded.

-Inclusion criteria are : patients between 18 and 85 years old with end stage knee osteoarthritis undergoing unilateral, primary TKA(total knee arthroplasty) -exclusion criteria are : opium sensitivity or ketamine contraindication Rheumatoid arthritis, patients unable to understand the visual analog scale previous history of knee arthroplasty, simultaneous bilateral arthroplasty patients receiving general anesthesia or a nerve block. body mass index greater than 40 kg/m2, preoperative ketamine or chronic narcotic usage discharged before the first 24 hour

group A(placebo): ketamine 0.5 mg per kg of patient body weight (total volume will be increased to 5 ml by adding normal saline) group B (drug): 5 ml of normal saline

post operative pain at 2,6,12,24 hour and 10 and 42 days post operation are evaluated. the time of first analgesic request.total analgesic consumption.duration of hospitalization,rate of complications,knee range of motion,patient satisfaction and subgroup analysis according to age,sex,deformity and stage of soft tissue release will be evaluated.

block randomization will be used to produce randomized sequences .each block will consists of 4 sites including 2 placebos(B) and 2 drugs(A).That way,6 randomization pattern(permutations of 2 from 4) will be available. Random choosing of the above mentioned sites will be performed based on www.randomization.org. and will be performed Hiddenly . The placebo/drug that each patient receives will be concealed from the physician, statistician and the patient. 30 concealed envelopes that contain instructions for mixing solutions for group A, and the other 30 for group B are put on each other. content of each envelope is based on previously instructed randomization pattern. After entering the patient to the operating room ,an anesthesiology technician not involving in other part of the study will choose the first envelope from the top and follow the instructions of preparing the syringe content. He then documents the patient's ID and predetermined group. thereafter, he does not partake in any subsequent part of the study .after data gathering and completion of the analysis,the A/B labels will be decoded to prepare the final manuscript. None of the other investigators involved in patient management or data collection is aware of the group assignment

60 identical sequentially numbered, opaque, sealed, and stapled envelopes(30 envelopes contain instructions for mixing solutions for group A, and the other 30 for group B) are put on each other. content of each envelope is based on previously instructed block randomization pattern. After entering the patient to the operating room ,an anesthesiology technician not involving in other part of the study will choose the first envelope from the top and follow the instructions of preparing the syringe content. The volume of each syringes will reaches 5 cc by adding normal saline so all of the injected syringes in A/B groups contains the same volume. Also, both ketamine and normal saline study solutions had the same physical properties: clear liquids with no distinctive odor .Therefore, they can not be identified or differentiated by sight or smell . The technician then documents the patient's characteristics and A/B intervention groups. The patient ,the surgeon and date collecting team members are blind of the injected liquid. After data gathering and completion of the analysis the A/B labels will be decoded to prepare the final manuscript.