Pain Management in Critical Combat Casualty Environments Using Resorbable Poly(ester Urea) Films for Sustained Delivery of Meloxicam and Bupivacaine
Abstract
Over the past two decades of military operations in Afghanistan and Iraq, > 51,000 U.S. Soldiers have been wounded in action in military operations, and these Soldiers often experience significant pain. Given the widespread impact of pain affecting Veterans, the U.S. military has made a substantial effort to collect information regarding the consequences and treatment of pain, and to apply that knowledge to provide better care for returning wounded Soldiers. Appropriate pain management also represents a major challenge in the general U.S. civilian population. New strategies that aid in the control of acute pain, especially non-opioid alternatives, are needed. Improvement of acute pain management for combat-related injuries in the military has largely focused on determining which pain control methods can be readily administered and provide adequate pain relief during immediate field hospital care, transport and subsequent care at military treatment facilities. The care that an injured Service Member receives can be divided based on the location and level of care. Level I care is the first-responder medical care that an injured Service Member receives on the battlefield, administered by either a Service Member or combat medic. The patient is then transported to a Level II care facility (or battlefield medical facility) or a Level III facility (or off-battlefield medical facility). Level IV (outside the U.S.) and Level V (in the U.S.) medical care facilities represent definitive care facilities. For moderate to severe pain, either oral opioids or ketamine may be used, depending on the presence of comorbid respiratory distress or hemorrhagic shock. Under-managed acute pain is known to be associated with an increased risk of certain complications and an increased risk of transition to a chronic pain state. Inadequate analgesia following injury has also been associated with an increased risk of post-traumatic stress disorder (PTSD) following combat-related injuries. Therefore, controlling acute pain is critical. The tools for acute pain control in far-forward environments are limited and remain a pressing need. Our proposal aims to address this need directly. Aims: In this proposal, we outline a strategy to co-deliver two non-opioid drugs (bupivacaine and meloxicam) from degradable polymer films. The two drugs target two different pain pathways (one for nerve conduction, and one for inflammation), which should provide more effective pain control than either drug by itself. The specific aims within this proposal are designed to drive the development of an implantable medical device in the form of drug-loaded degradable polymer film that would be easily deployable for critical combat casualty environments and control acute pain locally via the controlled and sustained release of non-opioid analgesics. The deployable and implantable medical device (paper-like film) would reduce and likely eliminate the need to prescribe opioids while effectively controlling post-traumatic and post-surgical pain by providing localized pain relief for 4-5 days. The aims will (1) optimize the concentrations of drugs in the film, (2) assess the safety in well-established mouse models of pain, and (3) look at the local vs. whole body drug concentrations of drug which will be critical to establish effective dosing and safety protocols. These films could be carried in critical combat casualty environments by combat medics and deployed at the site of injury. The onset of analgesia would be rapid locally but the risk of overdose or systemic toxicity would be extremely low, given very low serum levels of the loaded drugs. Bupivacaine and meloxicam target different sites of the pain pathway and together block multiple signaling pathways at the region where pain is originated. We hypothesize that targeting inflammation and nerve conduction simultaneously at the site of injury would result in more effective pain relief by targeting different mechanisms
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210646
Entities
People
- Ru-Rong Ji
Organizations
- Duke University
- United States Army