Clinical trial NCT02793947: Efficacy of Peri-Incisional Multimodal Drug Injection Following Operative Management of Femur Fractures
Official title: Efficacy of Peri-Incisional Multimodal Drug Injection Following Operative Management of Femur Fractures: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Postoperative
Femur Fracture
Keywords: Peri-incisional injection
Multimodal analgesia
Femur fracture
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2016-06-08
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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. Enrolled subjects will be prospectively randomized into either the peri-incisional injection or control cohorts. Patients will be treated with standard of care surgical techniques by the treating orthopaedic surgeon for the patient's specific fracture pattern. The patients randomized into the injection cohort will receive an intra-operative injection with 400 mg ropivacaine, 0.6 mg epinephrine, 5 mg and morphine into the local superficial and deep peri-incisional tissues while under general anesthesia. Visual analog pain scores will be collected every 4 hours after surgery for the first two post-operative days. Total narcotic consumption will also be recorded over eight hour intervals for the first two post-operative days. Medication related side effects will be monitored. The investigators hypothesize that the peri-incisional injection cohort will demonstrate an improved pain profile and utilize less parenteral narcotic analgesia in the early post-operative period.

Detailed description: 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.

The secondary outcome measures are total narcotic consumption, wound complications, and drug-related side effects. Narcotic consumption will be recorded every eight hours for the first two post-operative days and transformed into narcotic equivalents. Every fifteen minutes in the post-anesthesia care unit and every four hours for the first two post-operative days nursing personnel will monitor the patients via direct observation and query for medication side effects related to ropivacaine toxicity including blurred vision, hearing problems, transient peripheral paralysis, dizziness, convulsion, uncontrolled muscle contraction, hypotension, bradycardia, and new onset arrhythmia. Anesthesiology staff will also perform two standardized post-operative assessments in the recovery room and on the first post-operative day to screen for adverse effects related to the injection.

An a priori power analysis was completed for sample size determination for the primary outcome measure. A preliminary retrospective analysis revealed a standard deviation of 2.5 on the visual analog pain scale twelve hours following surgery (unpublished data). Prior literature has suggested that a change of 1.0-1.3 points on the visual analog scale is clinically significant. Therefore, the investigators determined a total of 44 patients were required per study group in order to detect a 1.5 point difference on the visual analog scale with a power of 80% and a P-value of 0.05. The Student t test and the chi-squared test of association will be used to compare continuous and categorical variables between the two groups, respectively. Statistical significance is defined as p \<0.05.

Patient confidentiality will be maintained at all times. Only approved research team personnel will review the medical records. Only the minimal data necessary to answer the research questions will be obtained. Collected electronic data will be stored on password protected servers. Written informed consent documents will be stored in a locked filing cabinet in the Department of Orthopaedics and Rehabilitation at the University of Iowa Hospitals and Clinics. Upon publication and completion of data analysis all information with patient identifiers will be destroyed.

Eligibility criteria: Inclusion Criteria:

* Patients who sustained an acute femur fracture in any anatomic region (subcapital, basicervical, intertrochanteric, subtrochanteric, diaphyseal, distal metaphyseal, or distal articular)
* Age ≥18 years
* Indicated for definitive operative management at a single Level 1 trauma center

Exclusion Criteria:

* Revision procedures
* Temporizing procedures (irrigation and debridement, external fixation)
* Regular narcotic use
* Psychiatric illness
* Dementia
* Neuromuscular deficit
* Allergy/intolerance to cocktail ingredients
* Clinical status that precludes verbal pain assessment (e.g. major intracranial trauma)
* Refusal to participate

Primary outcomes:
measure: Visual Analog Scale Pain Assessment
timeFrame: Pain assessment will be collected immediately prior to surgery (pre-op), immediately following surgery in the post-anesthesia care unit (PACU), and every 4 hours following surgery for the first two post-operative days (48 hours total; 4H-48H)
Secondary outcomes:
measure: Total Narcotic Consumption
timeFrame: Narcotic consumption will be recorded every 8 hours for the first two post-operative days.
Other outcomes:
measure: Number of Participants With Medication-related Side Effects
timeFrame: 48 hours following surgery
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
Study officials:
affiliation: University of Iowa
name: Michael C Willey, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vendittoli PA, Makinen P, Drolet P, Lavigne M, Fallaha M, Guertin MC, Varin F. A multimodal analgesia protocol for total knee arthroplasty. A randomized, controlled study. J Bone Joint Surg Am. 2006 Feb;88(2):282-9. doi: 10.2106/JBJS.E.00173.
citation: Busch CA, Shore BJ, Bhandari R, Ganapathy S, MacDonald SJ, Bourne RB, Rorabeck CH, McCalden RW. Efficacy of periarticular multimodal drug injection in total knee arthroplasty. A randomized trial. J Bone Joint Surg Am. 2006 May;88(5):959-63. doi: 10.2106/JBJS.E.00344.
citation: Busch CA, Whitehouse MR, Shore BJ, MacDonald SJ, McCalden RW, Bourne RB. The efficacy of periarticular multimodal drug infiltration in total hip arthroplasty. Clin Orthop Relat Res. 2010 Aug;468(8):2152-9. doi: 10.1007/s11999-009-1198-7. Epub 2009 Dec 18.
citation: Kang H, Ha YC, Kim JY, Woo YC, Lee JS, Jang EC. Effectiveness of multimodal pain management after bipolar hemiarthroplasty for hip fracture: a randomized, controlled study. J Bone Joint Surg Am. 2013 Feb 20;95(4):291-6. doi: 10.2106/JBJS.K.01708.