Inflammatory Markers in Trauma Patient Outcomes

Summary

It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced narcotic requirements in orthopaedic patient population, and improved patient subjective pain after hospital discharge. Preliminary animal and clinical studies have shown correlation between elevated blood cytokine concentrations during the acute phase of trauma and the development of post-traumatic complications. Early administration of nonsteroidal anti-inflammatory drug (NSAID) in animals significantly reduced inflammatory profiles, improved pulmonary edema, and enhanced arteriole vasoconstriction in response to hemorrhage. The ability to modify post-traumatic physiologic response via short-term administration of a non-steroidal anti-inflammatory drug (NSAID) may lead to improved patient outcome. In addition, given the current landscape for opioid epidemic in the United States, alternative non-opioid pain management during acute trauma has the potential to reduce opioid consumption and represents a pivotal component of multimodal analgesia strategy. By doing this study, the investigators hope to learn how to provide the best care for all patients in the state of Kentucky. Patient participation in this research will last about 1 year.

Timeline

Start

2019-02-28

Primary completion

2023-06-20

Completion

2023-06-20

Publications

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• Background Ellis TA 2nd, Hammoud H, Dela Merced P, Nooli NP, Ghoddoussi F, Kong J, Krishnan SH. Multimodal Clinical Pathway With Adductor Canal Block Decreases Hospital Length of Stay, Improves Pain Control, and Reduces Opioid Consumption in Total Knee Arthroplasty Patients: A Retrospective Review. J Arthroplasty. 2018 Aug;33(8):2440-2448. doi: 10.1016/j.arth.2018.03.053. Epub 2018 Mar 27.
• Background Johnson P, Hustedt J, Matiski T, Childers R, Lederman E. Improvement in Postoperative Pain Control and Length of Stay With Peripheral Nerve Block Prior to Distal Radius Repair. Orthopedics. 2020 Nov 1;43(6):e549-e552. doi: 10.3928/01477447-20200721-14. Epub 2020 Aug 6.
• Background Walker CT, Gullotti DM, Prendergast V, Radosevich J, Grimm D, Cole TS, Godzik J, Patel AA, Whiting AC, Little A, Uribe JS, Kakarla UK, Turner JD. Implementation of a Standardized Multimodal Postoperative Analgesia Protocol Improves Pain Control, Reduces Opioid Consumption, and Shortens Length of Hospital Stay After Posterior Lumbar Spinal Fusion. Neurosurgery. 2020 Jul 1;87(1):130-136. doi: 10.1093/neuros/nyz312.
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• Background Morris BJ, Mir HR. The opioid epidemic: impact on orthopaedic surgery. J Am Acad Orthop Surg. 2015 May;23(5):267-71. doi: 10.5435/JAAOS-D-14-00163.
• Background Rodriguez-Buitrago A, Attum B, Enata N, Evans A, Okwumabua E, Gajari V, Obremskey WT, Jahangir A. Opiate Prescribing Practices After Common Isolated Lower Extremity Injuries. J Orthop Trauma. 2019 Mar;33(3):e93-e99. doi: 10.1097/BOT.0000000000001375.
• Background Castillo RC, MacKenzie EJ, Wegener ST, Bosse MJ; LEAP Study Group. Prevalence of chronic pain seven years following limb threatening lower extremity trauma. Pain. 2006 Oct;124(3):321-329. doi: 10.1016/j.pain.2006.04.020. Epub 2006 Jun 15.
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• Background Frink M, Hsieh YC, Hsieh CH, Pape HC, Choudhry MA, Schwacha MG, Chaudry IH. Keratinocyte-derived chemokine plays a critical role in the induction of systemic inflammation and tissue damage after trauma-hemorrhage. Shock. 2007 Nov;28(5):576-81. doi: 10.1097/shk.0b013e31814b8e0d.
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• Background Sikka G, Miller KL, Steppan J, Pandey D, Jung SM, Fraser CD 3rd, Ellis C, Ross D, Vandegaer K, Bedja D, Gabrielson K, Walston JD, Berkowitz DE, Barouch LA. Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. Exp Gerontol. 2013 Feb;48(2):128-35. doi: 10.1016/j.exger.2012.11.001. Epub 2012 Nov 13.
• Background Vadivelu N, Chang D, Helander EM, Bordelon GJ, Kai A, Kaye AD, Hsu D, Bang D, Julka I. Ketorolac, Oxymorphone, Tapentadol, and Tramadol: A Comprehensive Review. Anesthesiol Clin. 2017 Jun;35(2):e1-e20. doi: 10.1016/j.anclin.2017.01.001. Epub 2017 Apr 14.
• Background Rogero MM, Calder PC. Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids. Nutrients. 2018 Mar 30;10(4):432. doi: 10.3390/nu10040432.
• Background Almahmoud K, Namas RA, Abdul-Malak O, Zaaqoq AM, Zamora R, Zuckerbraun BS, Sperry J, Peitzman AB, Billiar TR, Vodovotz Y. Impact of Injury Severity on Dynamic Inflammation Networks Following Blunt Trauma. Shock. 2015 Aug;44(2):101-9. doi: 10.1097/SHK.0000000000000395.
• Background Namas RA, Vodovotz Y, Almahmoud K, Abdul-Malak O, Zaaqoq A, Namas R, Mi Q, Barclay D, Zuckerbraun B, Peitzman AB, Sperry J, Billiar TR. Temporal Patterns of Circulating Inflammation Biomarker Networks Differentiate Susceptibility to Nosocomial Infection Following Blunt Trauma in Humans. Ann Surg. 2016 Jan;263(1):191-8. doi: 10.1097/SLA.0000000000001001.
• Background Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, Hayden DL, Hennessy L, Moore EE, Minei JP, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Brownstein BH, Mason PH, Baker HV, Finnerty CC, Jeschke MG, Lopez MC, Klein MB, Gamelli RL, Gibran NS, Arnoldo B, Xu W, Zhang Y, Calvano SE, McDonald-Smith GP, Schoenfeld DA, Storey JD, Cobb JP, Warren HS, Moldawer LL, Herndon DN, Lowry SF, Maier RV, Davis RW, Tompkins RG; Inflammation and Host Response to Injury Large-Scale Collaborative Research Program. A genomic storm in critically injured humans. J Exp Med. 2011 Dec 19;208(13):2581-90. doi: 10.1084/jem.20111354. Epub 2011 Nov 21.
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• Background Mazzocca AD, McCarthy MB, Intravia J, Beitzel K, Apostolakos J, Cote MP, Bradley J, Arciero RA. An in vitro evaluation of the anti-inflammatory effects of platelet-rich plasma, ketorolac, and methylprednisolone. Arthroscopy. 2013 Apr;29(4):675-83. doi: 10.1016/j.arthro.2012.12.005. Epub 2013 Feb 6.
• Background Zhang W, Mei R, Wu S. Ketorolac tromethamine represses senescence in aging articular chondrocytes. Biosci Biotechnol Biochem. 2022 Jun 25;86(7):837-845. doi: 10.1093/bbb/zbac047.
• Background Carvalho B, Lemmens HJ, Ting V, Angst MS. Postoperative subcutaneous instillation of low-dose ketorolac but not hydromorphone reduces wound exudate concentrations of interleukin-6 and interleukin-10 and improves analgesia following cesarean delivery. J Pain. 2013 Jan;14(1):48-56. doi: 10.1016/j.jpain.2012.10.002. Epub 2012 Dec 4.
• Background Kim MH, Hahm TS. Plasma levels of interleukin-6 and interleukin-10 are affected by ketorolac as an adjunct to patient-controlled morphine after abdominal hysterectomy. Clin J Pain. 2001 Mar;17(1):72-7. doi: 10.1097/00002508-200103000-00010.
• Background Singh P, Rastogi S, Bansal M, Kumar S, Singh R, Nishad SG, Reddy MP, Anand KR, Kumar S, Thayath MN. A prospective study to assess the levels of interleukin-6 following administration of diclofenac, ketorolac and tramadol after surgical removal of lower third molars. J Maxillofac Oral Surg. 2015 Jun;14(2):219-25. doi: 10.1007/s12663-013-0609-1. Epub 2014 Feb 18.
• Background Kuchalik J, Magnuson A, Tina E, Gupta A. Does local infiltration analgesia reduce peri-operative inflammation following total hip arthroplasty? A randomized, double-blind study. BMC Anesthesiol. 2017 May 3;17(1):63. doi: 10.1186/s12871-017-0354-y.
• Background Namas RA, Almahmoud K, Mi Q, Ghuma A, Namas R, Zaaqoq A, Zhu X, Abdul-Malak O, Sperry J, Zamora R, Billiar TR, Vodovotz Y. Individual-specific principal component analysis of circulating inflammatory mediators predicts early organ dysfunction in trauma patients. J Crit Care. 2016 Dec;36:146-153. doi: 10.1016/j.jcrc.2016.07.002. Epub 2016 Jul 11.
• Background Levy RM, Mollen KP, Prince JM, Kaczorowski DJ, Vallabhaneni R, Liu S, Tracey KJ, Lotze MT, Hackam DJ, Fink MP, Vodovotz Y, Billiar TR. Systemic inflammation and remote organ injury following trauma require HMGB1. Am J Physiol Regul Integr Comp Physiol. 2007 Oct;293(4):R1538-44. doi: 10.1152/ajpregu.00272.2007. Epub 2007 Jul 25.
• Background Giannoudis PV, Giannoudi M, Stavlas P. Damage control orthopaedics: lessons learned. Injury. 2009 Nov;40 Suppl 4:S47-52. doi: 10.1016/j.injury.2009.10.036.
• Background Billiar TR, Hunt BJ, Bailly S. Targeting inflammation in traumatic injury: entering a new era. Intensive Care Med. 2023 Aug;49(8):977-978. doi: 10.1007/s00134-023-07152-2. Epub 2023 Jul 19. No abstract available.
• Background Namas R, Ghuma A, Hermus L, Zamora R, Okonkwo DO, Billiar TR, Vodovotz Y. The acute inflammatory response in trauma / hemorrhage and traumatic brain injury: current state and emerging prospects. Libyan J Med. 2009 Sep 1;4(3):97-103. doi: 10.4176/090325.
• Background Giannoudis PV, Hak D, Sanders D, Donohoe E, Tosounidis T, Bahney C. Inflammation, Bone Healing, and Anti-Inflammatory Drugs: An Update. J Orthop Trauma. 2015 Dec;29 Suppl 12:S6-9. doi: 10.1097/BOT.0000000000000465.
• Background Dodwell ER, Latorre JG, Parisini E, Zwettler E, Chandra D, Mulpuri K, Snyder B. NSAID exposure and risk of nonunion: a meta-analysis of case-control and cohort studies. Calcif Tissue Int. 2010 Sep;87(3):193-202. doi: 10.1007/s00223-010-9379-7. Epub 2010 Jun 15.
• Results Foster JA, Kavolus MW, Landy DC, Pectol RW, Sneed CR, Kinchelow DL, Griffin JT, Hawk GS, Bernard AC, Oyler DR, Aneja A. Low-Dose Short-Term Scheduled Ketorolac Reduces Opioid Use and Pain in Orthopaedic Polytrauma Patients: A Randomized Clinical Trial. J Orthop Trauma. 2023 Dec 1;37(12):633-639. doi: 10.1097/BOT.0000000000002703.
• Results Foster JA, Hawk GS, Landy DC, Griffin JT, Bernard AC, Oyler DR, Southall WGS, Muhammad M, Sierra-Arce CR, Mounce SD, Borgida JS, Xiang L, Aneja A. Does Scheduled Low-Dose Short-Term NSAID (Ketorolac) Modulate Cytokine Levels After Orthopaedic Polytrauma? A Secondary Analysis of a Randomized Clinical Trial. J Orthop Trauma. 2024 Jul 1;38(7):358-365. doi: 10.1097/BOT.0000000000002807.

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