Efficacy of Multimodal Periarticular Injections in Operatively Treated Ankle Fractures

Efficacy of Multimodal Periarticular Injections in Operatively Treated Ankle Fractures: A Randomized Controlled Trial

The purpose of this study is to determine the efficacy and safety of a peri-articular multimodal injection for post-operative pain control following operative management of closed, rotational ankle fractures. Enrolled subjects will be randomized to either receive or not receive intra-operative injections in addition to standard opioid analgesic regimens. 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 a 25cc intra-operative injection with 200 mg ropivacaine, 0.6 mg epinephrine, 5 mg and morphine into the local superficial and deep peri-incisional tissues while under general anesthesia. Total post-operative opioid consumption expressed in morphine equivalent dose will be recorded, including IV and oral opioids. Time in hours from operation conclusion to discharge and discharge disposition (to where the patient is discharged) will also be recorded. Post-operative pain scores will be assessed and recorded in the immediate post-operative period and every 4 hours subsequently until the patient is discharged. Medication related side effects will be monitored. The investigators hypothesize that the injection cohort will have reduced pain scores, lower narcotic requirements, shorter length of stay, and be more likely to discharge to home following surgery.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Ankle Fractures
• Intervention / Treatment: Drug: Morphine; Drug: Ropivacaine; Drug: Epinephrine; Drug: 0.9% sodium chloride solution

Detailed Description

Periarticular fractures (bone breaks extending into the joint surface) treated by orthopaedic surgeons are associated with significant pain in the post-operative period, often requiring high doses of opioid analgesics. In recent years, the high risk of misuse, abuse, and death associated with prescription opioid use has become increasingly evident.

Although physicians are being advised to avoid administration of opioid prescriptions, alternative pain management options are limited. Currently, there is a need to investigate different pain management models in order to provide safe and effective pain relief during the post-operative period. The investigators aim to evaluate the effectiveness of peri-incisional multimodal injections as an alternative post-operative pain control method in orthopaedic trauma patients with operative ankle fractures. Approximately 200 patients will be randomized to either receive or not receive intra-operative injections in addition to standard opioid analgesic regimens. Post-operative pain management outcomes will be assessed and compared between the 2 study groups to determine effectiveness of the injections. The proposed study will build upon related work to advance post-operative pain control regimens in orthopaedic surgery. Goals include the reduction of unnecessary patient suffering, reliance on opioids, and length of stay, while improving patient experience. These aims will be accomplished through the expansion of currently used multimodal periarticular injections from populations undergoing elective surgery to orthopaedic trauma patients with rotational ankle fractures.

The study design is a prospective, double-blinded, randomized controlled trial. Patients included in the study will be randomly assigned to one of two treatment groups: intra-operative multimodal periarticular injection or control (no injection). The peri-incisional injection will consist of ropivacaine, epinephrine, and morphine. All pharmacologic agents in the anesthetic cocktail are FDA approved and have been previously used in combination during other types of orthopaedic surgeries.

All patients included in the study will receive standard post-operative opioid analgesic regimens, administered 'per needed', regardless of their assigned treatment group per study protocol. ≥ 40 patients will be randomly assigned to each group. The patients enrolled in the investigation as well as health care professionals performing post-operative assessments and collecting data will be blinded to treatment allocation. The feasibility of multimodal peri-incisional injections is supported by their current efficacy in populations undergoing elective orthopedic surgeries. These injections may be equally effective at reducing pain compared to regional anesthesia with continuous infusions, and single-shot nerve blocks.

The investigators hypothesize that the injection cohort will have reduced pain scores, lower narcotic requirements, shorter length of stay, and be more likely to discharge to home following surgery.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All consenting patients 18 years of age and older with operative, closed, rotational ankle fractures treated with internal fixation.

Exclusion Criteria:

• Patients with any of the following:

  • Allergy or medical contraindication to any of the study medications
  • Pregnant women
  • Diagnosed dementia
  • Preexisting opioid or illicit drug dependency
  • Major neuromuscular deficit
  • Severe systemic disorder (heart failure, respiratory failure, kidney failure, liver failure, or a clotting disorder)
  • Major head trauma
  • Concomitant distracting injury
  • Other surgical intervention in the study period (1 week)
  • Revision operations
  • Insists to receive peripheral nerve blocks for surgical anesthesia
  • Refusal to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Peri-incisional injection; A single, 25 cc multimodal analgesic cocktail will be injected following completion of ankle fracture fixation/instrumentation while the patient remains under general anesthesia and prior to skin closure. The injection will be administered as such: 20 mL injected into the peri-incisional soft tissues in a circumferential fashion; 5mL injected into the ankle joint This cocktail includes 200 mg of 0.8% ropivacaine, 0.6 mg of epinephrine, 5 mg of morphine sulfate, and sodium chloride solution. All infiltrations will be completed with a blunt trochar to minimize the risk of intravascular injection. Interventions: Drug: Ropivacaine Drug: Epinephrine Drug: Morphine Drug: 0.9% sodium chloride solution Following surgery, patients in the treatment and non-treatment groups will both be provided with the same intravenous (patient-controlled analgesia) and oral pain medications scheduled "per needed".	Drug: Morphine; Other Names: Duramorph; Drug: Ropivacaine; Other Names: Naropin; Drug: Epinephrine; Other Names: Adrenalin; Drug: 0.9% sodium chloride solution; Other Names: 0.9% normal saline
No Intervention: Control; Ankle fracture fixation/instrumentation will be completed per the standard of care. No peri-incisional injection will be completed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Post-operative Visual Analog Pain Scores (VAS)	The primary outcome was VAS pain over the first 48 hours postoperatively. Patients reported pain with use of a 100-mm VAS, with 0-mm being no pain and 100-mm being the most extreme pain imaginable. A higher score indicates worse pain. Scores were reported as mean values at 24 hours post-surgery and 48 hours post-surgery.	Immediately following surgery, then every 4 hours following surgery for 48 hours post-surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Use in First 24 Hours Post-surgery	Total opioid consumption expressed in morphine equivalent dose will be recorded, including IV and oral opioids, in the first 24 hours post-surgery.	At 24 hours post-surgery & during the total time of inpatient stay to dischage
Post-operative Length of Stay	Number of days in the hospital following surgery	From immediately following surgery to 90 days after.
Patients Returning Home Following Surgery	Number of patients returning to their home following discharge, vs. going to a rehabilitation or skilled nursing facility	Following hospital discharge from surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication-related Side Effects	Patients will be monitored by nursing personnel 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.	From immediately following surgery to 7 days after.

Collaborators and Investigators

• Sponsor: University of Iowa
• Investigators: Principal Investigator: Kyle Hancock, MD, Resident Physician

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): September 21, 2018
• Study Completion (Actual): September 21, 2018

Study Registration Dates

• First Submitted: October 27, 2016
• First Submitted That Met QC Criteria: November 15, 2016
• First Posted (Estimated): November 18, 2016

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Wounds and Injuries; Leg Injuries; Ankle Injuries; Pain, Postoperative; Fractures, Bone; Ankle Fractures; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Anesthetics, Local; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Ropivacaine; Morphine; Epinephrine
• Other Study ID Numbers: 201608737

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes