Efficacy of Peri-Incisional Multimodal Drug Injection Following Operative Management of Femur Fractures: A Randomized Controlled Trial

The purpose of this study is to determine the efficacy and safety of a peri-incisional multimodal injection for post-operative pain control following operative management of femur fractures. Patients will be identified by way of direct presentation to the orthopaedic trauma service with an acute femur fracture. If the patient meets the parameters for study enrollment (inclusion/exclusion criteria) the patient will be approached for introduction of the study by a member of the surgical team. If the patient is agreeable to study enrollment, he/she will have to complete the written informed consent process. This study protocol has received formal approval from the University of Iowa Institutional Review Board.

The study design is a prospective, randomized, double-blind comparative trial. Patients will be randomly assigned to the two treatment groups: peri-incisional multimodal injection and control (no injection). In order to create balanced cohorts with respect to intervention, randomization will be completed in a block format across six discrete surgical techniques: proximal femur open reduction and internal fixation (dynamic hip screw, trochanteric stabilizing plate), distal femur open reduction and internal fixation (lateral peri-articular locking plate), cephalomedullary fixation, other intramedullary fixation (antegrade or retrograde intramedullary device without fixed angle construct into the femoral head), percutaneous fixation, and arthroplasty (hemiarthroplasty or total hip arthroplasty). Randomization will be performed with use of Microsoft Excel (Microsoft, Redmond, Washington) to generate random numbers. The patients enrolled in the investigation as well as the nursing staff performing the post-operative assessments are blinded to treatment allocation.

Each patient will be treated with standard of care techniques chosen by the treating surgeon regardless of whether or not the patient decides to enroll in the study. Written informed consent will be obtained for the surgical procedure in addition to and independent from the study consent. All surgical procedures will be completed under general anesthesia. No spinal, regional, or preemptive anesthesia/analgesic regimen will be employed per study protocol. Surgical drain placement and pharmacologic venous thromboembolism prophylaxis will not be standardized. Post-operative pain management will continue per the institutional standard of care with a combination of intravenous and oral narcotic analgesia. The post-operative pain regimen will not be specified nor altered by the study protocol.

Patients randomized to the peri-incisional injection cohort will receive a single intra-operative injection while the subject is under general anesthesia following completion of fracture fixation/instrumentation. The local anesthetic cocktail includes 400 mg of 0.75% ropivacaine (53.33 mL), 0.6 mg of 1 mg/mL epinephrine (0.6 mL), 5 mg of 0.5 mg/mL morphine sulfate (10 mL), and 36.07 mL 0.9% sodium chloride solution. All pharmacologic agents in the anesthetic cocktail are FDA approved. For intra-articular proximal femur procedures the cocktail will be evenly distributed between the deep (synovium, capsule, periosteum, gluteus musculature) and superficial (fascia lata, vastus lateralis, subcutaneous plane) tissues prior to wound closure. The same pattern will be followed for extra-articular proximal femur procedures without direct injection of the synovium and capsule. The injection will be similarly distributed between the deep (synovium, capsule, periosteum) and superficial (quadriceps musculature, subcutaneous plane) tissues prior to wound closure for distal femur procedures. Injections for intramedullary nails will be placed around the nail entry site into bone and into the superficial tissues at both the entry site and cross lock locations. All infiltrations will be completed with a blunt trochar to minimize the risk of intravascular injection.

The primary outcome is visual analog pain scores over the first two post-operative days. Patients will be instructed to use a 10-cm visual analog scale to describe their current level of comfort with end points of zero corresponding to "no pain" and ten corresponding to "the most extreme possible pain." Pain assessments will be completed while patients are at rest at standardized intervals immediately prior to surgery, in the post-anesthesia care unit (captured as the mean of all individual data points), and every 4 hours following surgery for the first two post-operative days. Visual analog pain scores are collected and charted by nursing staff on the inpatient ward. All nursing staff will remain blinded to the treatment allocation. Physician staff that have knowledge of the intra-operative treatment and randomization are not involved in recording any outcome measures.