ClinicalTrials.gg
Sign In
CompletedNCT03671746Updated Jun 5, 2025Results posted

Inflammatory Markers in Trauma Patient Outcomes

A Phase 1 interventional study of Ketorolac and Saline Solution in Polytrauma, sponsored by Arun Aneja. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-06-05.

Sponsored by Arun Aneja · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
70
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

Read the detailed description

Accidental trauma is the 4th leading cause of death in the United States, and it is associated with a complex inflammatory response. This response is associated with post-traumatic complications such as; multi-organ dysfunction syndrome (MODS), bacterial pneumonia, acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS), and post-traumatic pain (PTP). It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced narcotic requirements, and improved patient subjective pain after hospital discharge.

Preliminary data has shown: (1) elevated blood cytokine concentrations during the acute phase of trauma are correlated with the development of fatal post-traumatic complications, (2) that early administration of a non-steroidal anti-inflammatory drug (NSAID) resulted in decreased blood serum levels of interleukin (IL-6), Prostaglandin E2 (PGE2), improved pulmonary edema, and enhanced arterioles ability to vasoconstrict in response to hemorrhage in animal models, and (3) that the addition of the internal physiologic parameters (inflammatory cytokines) to New Injury Severity Score (NISS - a marker of the external anatomical insult) significantly improves the ability to predict hospital length of stay of trauma patients when compared to NISS alone. The investigator's group is the first to use an integrative approach that combines the external anatomic injury data with the internal physiologic response for accurate prediction of a patient's clinical outcome. Therefore, if the investigators apply this same mindset to treatment, the investigators can improve the trauma patients' care by addressing both parameters as opposed to solely focusing on the external injury as done in the past. The ability to modify post-traumatic physiologic response via short-term administration of an NSAID may lead to improved patient outcomes.

Over the last decade, clinicians have remained puzzled over the safety of NSAID administration after fracture in terms of bone union. In addition, given the current landscape for the 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.

02

Conditions studied

  • Polytrauma

Keywords

  • Inflammatory cytokine
  • inflammation
  • trauma
  • opioid
03

In context

Multiple Trauma

139 studies on the registry are indexed under Multiple Trauma; 32 are open to participants now.

This study's enrollment of 70 is below the median of 94 across 50 interventional studies indexed under Multiple Trauma.

Browse Multiple Trauma studies →

Lead sponsor

This is the only study on the registry with Arun Aneja as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients age 18 to 75
  • New Injury Severity Score (NISS) > 9, with musculoskeletal injury requiring surgical treatment

Exclusion criteria

Exclusion Criteria:

  • Patient age \< 18 or > 75
  • Patients who presented more than 24 hours after time of injury
  • Patients with to NSAID therapy (i.e., patients with active hemorrhage, received blood products, traumatic brain injury (TBI), active gastrointestinal bleeding or ulceration, NSAID allergy, thromboembolism, or coagulopathy)
  • Patients with pre-existing inflammatory condition (e.g., inflammatory arthropathy or bowel disease)
  • Patients with preexisting /immunosuppressed condition or acquired immunodeficiency syndrome (AIDS)
  • Patients with pre-existing comorbidities (e.g., coronary artery disease, myocardial infarction, chronic organ failure, , emphysema, asthma, etc.)
  • Patients with chronic use of , immuno-modulating drugs, or history of organ transplantation
  • Patients receiving chronic opioid therapy or treatment for opioid use disorder
  • Patients who are pregnant
  • Patients with thermal injury
Terms in these criteria, in plain language(4)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

COPD

Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
70 participants (actual)

Study arms

  • Placebo comparator
    Standard of Care without NSAID

    Polytrauma participants will receive standard of care in addition to saline solution according to standard Advanced Trauma Life Support (ATLS) and standard ICU routine medical care.

    Drug: Saline Solution

  • Experimental
    Standard of Care with NSAID

    Participants in the group will receive Ketorolac in addition to standard of care for the standard Advanced Trauma Life Support (ATLS) and standard ICU routine medical care.

    Drug: Ketorolac

Interventions

  • DrugKetorolac

    Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization

    Also known as: Toradol

  • DrugSaline Solution

    Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization

    Also known as: Normal Saline

06

What researchers measure

Primary outcomes

  1. Length of Hospital Stay

    Duration of the hospital stay will be calculated from electronic health record

    Time frame: Up to 30 days

Secondary outcomes

  1. Morphine Milligram Equivalents in House

    The the morphine milligram equivalents (MME) will be recorded throughout the course of the hospital stay. These will be reported as daily totals.

    Time frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

  2. Change in Patient Pain Scores

    The patient reported pain scores (visual analogue pain scores) will be recorded throughout the course of the hospital stay. The scores are reported by the patients and range from 0 indicating no pain to 100 meaning the worst pain imaginable. These will be reported as daily averages.

    Time frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

  3. Change in Interleukin 1a

    Daily blood collections during the first 5 days of hospitalization. Interleukin 1a will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 1 from presentation to the emergency room to day 5 of hospitalization.

    Time frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

  4. Change in Interleukin 1b

    Daily blood collections during the first 5 days of hospitalization. Interleukin 1b will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 1 from presentation to the emergency room to day 5 of hospitalization.

    Time frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

  5. Change in Interleukin 6

    Daily blood collections during the first 5 days of hospitalization. Interleukin 6 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 6 from presentation to the emergency room to day 5 of hospitalization.

    Time frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

  6. Change in Interleukin 10

    Daily blood collections during the first 5 days of hospitalization. Interleukin 10 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 10 from presentation to the emergency room to day 5 of hospitalization.

    Time frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

  7. Change in Prostaglandin E-2

    Blood will be collected over the course of 5 days of hospitalization. Prostaglandin E-2 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Prostaglandin E-2 from presentation to the emergency room to day 5 of hospitalization

    Time frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

  8. Post Traumatic Complications

    The Incidence of post-traumatic complications in the patients which includes, but is not limited to the occurrence of pulmonary complications (i.e., bacterial pneumonia, pulmonary edema, acute respiratory failure) and AKI will be recorded throughout the duration of the hospital stay, usually up to 30 days. Data will be presented as the percentage of participants with a diagnosed post-traumatic complication.

    Time frame: Up to 30 days

  9. Mortality

    The Incidence of death related to the initial trauma/traumatic complications will be recorded for the first 30 days.

    Time frame: Up to 30 days

  10. Change in Inpatient Subjective Pain Reports

    The patient reported pain scores (visual analogue pain scores) will be recorded throughout the course of the hospital stay. The scores are reported by the patients and range from 0 indicating no pain to 100 meaning the worst pain imaginable. These will be reported as daily averages.

    Time frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

  11. Change in Outpatient Subjective Pain Reports

    Patient reports of level of pain and how much it inhibits their daily activities will be recorded in the outpatient setting. The scores are reported by the patients (visual analogue scale) and range from 0 indicating no pain to 100 meaning the worst pain imaginable. This will be reported for each patient follow-up visit. Several visits are possible and data will only be collected for the first year of follow-up. Data presented as the change in subject pain from baseline to 365 days.

    Time frame: up to 365 days

07

Results

Posted Jun 5, 2025
Limitations and caveats
The study was unable to achieve the target enrollment of 56 patients per group due to the institution suspending all clinical trial enrollment during the COVID-19 pandemic. Blood samples were not able to be collected from two patients and clinical outcomes for one patient. Due to a transition in the institution's electronic medical record that occurred in 2021, one patient's chart could not be recovered, hence clinical outcomes could not be collected for this patient.

Participant flow

After obtaining institutional review board approval at a single Level I trauma center and clinical trial registration (ClinicalTrials.gov; NCT03671746), potential subjects were screened, recruited, and enrolled from February 2019 to October 2022. The types of locations in which participants were enrolled included the institution's emergency department, pre-operative holding area, or hospital unit.

Participant flow — Overall Study
MilestoneStandard of Care Without NSAIDStandard of Care With NSAID
Started3535
Completed3535
Not completed00

Outcome measures

PrimaryLength of Hospital Stay

Duration of the hospital stay will be calculated from electronic health record

Time frame:
Up to 30 days
Reported as:
Median · days
Length of Hospital Stay
daysStandard of Care Without NSAIDStandard of Care With NSAID
Length of Hospital Stay7 (3 to 10)8 (4.5 to 11.5)
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · ANOVA · p = =0.275 · Median difference (final values): 1.5A Kenward-Roger adjustment was used to correct for negative bias in the standard errors and degrees of freedom calculations.
SecondaryMorphine Milligram Equivalents in House

The the morphine milligram equivalents (MME) will be recorded throughout the course of the hospital stay. These will be reported as daily totals.

Time frame:
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Reported as:
Median · morphine milligram equivalents
Morphine Milligram Equivalents in House
morphine milligram equivalentsStandard of Care Without NSAIDStandard of Care With NSAID
Day 0 (Enrollment)82.5 (49 to 118)86 (38 to 120)
Day 167.75 (48 to 81)48.75 (19 to 82)
Day 262 (38 to 90)53 (26 to 75)
Day 372 (45 to 99)38.25 (28 to 75)
Day 460 (28 to 78)30 (23 to 60)
Day 563.75 (32 to 88)30 (18 to 52)
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · Mixed Models Analysis · p = <0.05A Kenward-Roger adjustment was used to correct for negative bias in the standard errors and degrees of freedom calculations.
SecondaryChange in Patient Pain Scores

The patient reported pain scores (visual analogue pain scores) will be recorded throughout the course of the hospital stay. The scores are reported by the patients and range from 0 indicating no pain to 100 meaning the worst pain imaginable. These will be reported as daily averages.

Time frame:
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Reported as:
Mean · score on a scale
Change in Patient Pain Scores
score on a scaleStandard of Care Without NSAIDStandard of Care With NSAID
Day 0 (Enrollment)55.1 ± 27.568.2 ± 24.4
Day 152.2 ± 31.342.7 ± 25.6
Day 253.9 ± 26.547.4 ± 27.7
Day 354.1 ± 27.356.3 ± 26.0
Day 459.5 ± 26.943.3 ± 24.0
Day 559.2 ± 25.652.6 ± 21.9
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · Mixed Models Analysis · p = <0.05The VAS model was adjusted for baseline levels as a covariate, which differed significantly between groups.
SecondaryChange in Interleukin 1a

Daily blood collections during the first 5 days of hospitalization. Interleukin 1a will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 1 from presentation to the emergency room to day 5 of hospitalization.

Time frame:
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Reported as:
Median · fg/mL
Change in Interleukin 1a
fg/mLStandard of Care Without NSAIDStandard of Care With NSAID
Day 0 (Enrollment)115.1 (82 to 164)138.8 (65 to 177)
Day 1112.7 (72 to 176)122.6 (79 to 169)
Day 2119.3 (78 to 179)135.4 (60 to 207)
Day 3104.2 (76 to 153)135.0 (45 to 189)
Day 4150.2 (74 to 180)85.2 (23 to 203)
Day 5101.9 (65 to 162)148.7 (77 to 176)
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · Mixed Models Analysis · p = =0.564A Kenward-Roger adjustment was used to correct for negative bias in the standard errors and degrees of freedom calculations.
SecondaryChange in Interleukin 1b

Daily blood collections during the first 5 days of hospitalization. Interleukin 1b will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 1 from presentation to the emergency room to day 5 of hospitalization.

Time frame:
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Reported as:
Median · pg/mL
Change in Interleukin 1b
pg/mLStandard of Care Without NSAIDStandard of Care With NSAID
Day 0 (Enrollment)0.119 (0.073 to 0.165)0.119 (0.085 to 0.187)
Day 10.095 (0.043 to 0.184)0.130 (0.070 to 0.199)
Day 20.084 (0.058 to 0.132)0.118 (0.080 to 0.230)
Day 30.091 (0.068 to 0.141)0.108 (0.072 to 0.276)
Day 40.064 (0.048 to 0.097)0.166 (0.091 to 0.216)
Day 50.056 (0.043 to 0.071)0.126 (0.081 to 0.184)
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · Mixed Models Analysis · p = =0.118A Kenward-Roger adjustment was used to correct for negative bias in the standard errors and degrees of freedom calculations.
SecondaryChange in Interleukin 6

Daily blood collections during the first 5 days of hospitalization. Interleukin 6 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 6 from presentation to the emergency room to day 5 of hospitalization.

Time frame:
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Reported as:
Median · pg/mL
Change in Interleukin 6
pg/mLStandard of Care Without NSAIDStandard of Care With NSAID
Day 0 (Enrollment)21.5 (16 to 27)20.6 (13 to 25)
Day 121.2 (10 to 38)14.6 (8 to 34)
Day 216.3 (8 to 26)11.9 (6 to 18)
Day 312.9 (6 to 20)11.2 (6 to 27)
Day 47.9 (6 to 15)10.5 (7 to 23)
Day 510.5 (8 to 20)10.8 (5 to 26)
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · Mixed Models Analysis · p = 0.215A Kenward-Roger adjustment was used to correct for negative bias in the standard errors and degrees of freedom calculations.
SecondaryChange in Interleukin 10

Daily blood collections during the first 5 days of hospitalization. Interleukin 10 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 10 from presentation to the emergency room to day 5 of hospitalization.

Time frame:
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Reported as:
Median · pg/mL
Change in Interleukin 10
pg/mLStandard of Care Without NSAIDStandard of Care With NSAID
Day 0 (Enrollment)1.10 (0.7 to 1.7)1.11 (0.8 to 2.3)
Day 10.90 (0.6 to 1.6)0.76 (0.5 to 1.1)
Day 20.57 (0.4 to 1.3)0.62 (0.4 to 1.1)
Day 30.65 (0.5 to 0.9)0.64 (0.5 to 1.5)
Day 40.49 (0.4 to 0.8)0.59 (0.5 to 0.9)
Day 50.72 (0.4 to 1.3)0.75 (0.4 to 1)
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · Mixed Models Analysis · p = =0.043A Kenward-Roger adjustment was used to correct for negative bias in the standard errors and degrees of freedom calculations
SecondaryChange in Prostaglandin E-2

Blood will be collected over the course of 5 days of hospitalization. Prostaglandin E-2 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Prostaglandin E-2 from presentation to the emergency room to day 5 of hospitalization

Time frame:
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Reported as:
Median · pg/mL
Change in Prostaglandin E-2
pg/mLStandard of Care Without NSAIDStandard of Care With NSAID
Day 0 (Enrollment)352.2 (161 to 673)448.3 (232 to 738)
Day 1477.0 (309 to 810)375.8 (292 to 587)
Day 2345.8 (178 to 563)356.6 (209 to 509)
Day 3319.8 (239 to 605)371.3 (251 to 515)
Day 4347.6 (189 to 379)304.7 (237 to 430)
Day 5266.9 (209 to 475)322.3 (183 to 540)
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · Mixed Models Analysis · p = =0.617A Kenward-Roger adjustment was used to correct for negative bias in the standard errors and degrees of freedom calculations.
SecondaryPost Traumatic Complications

The Incidence of post-traumatic complications in the patients which includes, but is not limited to the occurrence of pulmonary complications (i.e., bacterial pneumonia, pulmonary edema, acute respiratory failure) and AKI will be recorded throughout the duration of the hospital stay, usually up to 30 days. Data will be presented as the percentage of participants with a diagnosed post-traumatic complication.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Post Traumatic Complications
ParticipantsStandard of Care Without NSAIDStandard of Care With NSAID
Pulmonary Complications43
Acute Kidney Injury (AKI)20
SecondaryMortality

The Incidence of death related to the initial trauma/traumatic complications will be recorded for the first 30 days.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Mortality
ParticipantsStandard of Care Without NSAIDStandard of Care With NSAID
Mortality00
Statistical analysis
  • Standard of Care Without NSAID vs Standard of Care With NSAID · Mixed Models Analysis · p = <0.05A Kenward-Roger adjustment was used to correct for negative bias in the standard errors and degrees of freedom calculations.
SecondaryChange in Inpatient Subjective Pain Reports

The patient reported pain scores (visual analogue pain scores) will be recorded throughout the course of the hospital stay. The scores are reported by the patients and range from 0 indicating no pain to 100 meaning the worst pain imaginable. These will be reported as daily averages.

Time frame:
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Reported as:
Mean · score on a scale
Change in Inpatient Subjective Pain Reports
score on a scaleStandard of Care Without NSAIDStandard of Care With NSAID
Day 0 (Enrollment)55.1 ± 27.568.2 ± 24.4
Day 152.2 ± 31.342.7 ± 25.6
Day 253.9 ± 26.547.4 ± 27.7
Day 354.1 ± 27.356.3 ± 26.0
Day 459.5 ± 26.943.3 ± 24.0
Day 559.2 ± 25.652.6 ± 21.9
SecondaryChange in Outpatient Subjective Pain Reports

Patient reports of level of pain and how much it inhibits their daily activities will be recorded in the outpatient setting. The scores are reported by the patients (visual analogue scale) and range from 0 indicating no pain to 100 meaning the worst pain imaginable. This will be reported for each patient follow-up visit. Several visits are possible and data will only be collected for the first year of follow-up. Data presented as the change in subject pain from baseline to 365 days.

Time frame:
up to 365 days
Reported as:
Mean · units on a scale
Change in Outpatient Subjective Pain Reports
units on a scaleStandard of Care Without NSAIDStandard of Care With NSAID
Change in Outpatient Subjective Pain Reports-22.7 (-40 to -1)-16.7 (-60 to -12)

Adverse events

Collected over Up to 30 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Standard of Care Without NSAID0/35 (0%)0/35 (0%)6/35 (17.1%)
Standard of Care With NSAID0/35 (0%)0/35 (0%)3/35 (8.6%)
Most frequent other events
Most frequent other events
EventStandard of Care Without NSAIDStandard of Care With NSAID
Pulmonary ComplicationsRespiratory, thoracic and mediastinal disorders4/353/35
Acute Kidney InjuryRenal and urinary disorders2/350/35

Baseline characteristics

Age, Continuous
Age, Continuous(years)Standard of Care Without NSAIDStandard of Care With NSAIDTotal
Mean40.0 ± 16.239.5 ± 17.239.8 ± 16.6
Sex: Female, Male
Sex: Female, Male(Participants)Standard of Care Without NSAIDStandard of Care With NSAIDTotal
Female111425
Male242145
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Standard of Care Without NSAIDStandard of Care With NSAIDTotal
Hispanic or Latino000
Not Hispanic or Latino353570
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Standard of Care Without NSAIDStandard of Care With NSAIDTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American224
White333366
More than one race000
Unknown or Not Reported000
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)Standard of Care Without NSAIDStandard of Care With NSAIDTotal
Mean29.5 ± 6.428.2 ± 7.328.9 ± 6.8
New Injury Severity Score (NISS)
New Injury Severity Score (NISS)(units on a scale)Standard of Care Without NSAIDStandard of Care With NSAIDTotal
Mean15.1 ± 6.414.0 ± 5.214.6 ± 5.8
Surgery Count
Surgery Count(number of surgeries)Standard of Care Without NSAIDStandard of Care With NSAIDTotal
Mean1.4 ± 0.71.2 ± 0.61.3 ± 0.6
08

Study locations

1 site
  • University of Kentucky
    Lexington, Kentucky 40536, United States
09

References and documents

Publications

  • Braden JB, Fan MY, Edlund MJ, Martin BC, DeVries A, Sullivan MD. Trends in use of opioids by noncancer pain type 2000-2005 among Arkansas Medicaid and HealthCore enrollees: results from the TROUP study. J Pain. 2008 Nov;9(11):1026-35. doi: 10.1016/j.jpain.2008.06.002. Epub 2008 Jul 26. PubMed 18676205 ↗
  • Lawal OD, Gold J, Murthy A, Ruchi R, Bavry E, Hume AL, Lewkowitz AK, Brothers T, Wen X. Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Jun 1;3(6):e207367. doi: 10.1001/jamanetworkopen.2020.7367. PubMed 32584407 ↗
  • Mohamadi A, Chan JJ, Lian J, Wright CL, Marin AM, Rodriguez EK, von Keudell A, Nazarian A. Risk Factors and Pooled Rate of Prolonged Opioid Use Following Trauma or Surgery: A Systematic Review and Meta-(Regression) Analysis. J Bone Joint Surg Am. 2018 Aug 1;100(15):1332-1340. doi: 10.2106/JBJS.17.01239. PubMed 30063596 ↗
  • Bosse MJ, MacKenzie EJ, Kellam JF, Burgess AR, Webb LX, Swiontkowski MF, Sanders RW, Jones AL, McAndrew MP, Patterson BM, McCarthy ML, Travison TG, Castillo RC. An analysis of outcomes of reconstruction or amputation after leg-threatening injuries. N Engl J Med. 2002 Dec 12;347(24):1924-31. doi: 10.1056/NEJMoa012604. PubMed 12477942 ↗
  • Castillo RC, MacKenzie EJ, Webb LX, Bosse MJ, Avery J; LEAP Study Group. Use and perceived need of physical therapy following severe lower-extremity trauma. Arch Phys Med Rehabil. 2005 Sep;86(9):1722-8. doi: 10.1016/j.apmr.2005.03.005. PubMed 16181933 ↗
  • O'Toole RV, Castillo RC, Pollak AN, MacKenzie EJ, Bosse MJ; LEAP Study Group. Determinants of patient satisfaction after severe lower-extremity injuries. J Bone Joint Surg Am. 2008 Jun;90(6):1206-11. doi: 10.2106/JBJS.G.00492. PubMed 18519312 ↗
  • Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003 Aug;97(2):534-540. doi: 10.1213/01.ANE.0000068822.10113.9E. PubMed 12873949 ↗
  • Sherwood GD, McNeill JA, Starck PL, Disnard G. Changing acute pain management outcomes in surgical patients. AORN J. 2003 Feb;77(2):374, 377-80, 384-90 passim. doi: 10.1016/s0001-2092(06)61206-4. PubMed 12619852 ↗
  • Hsu JR, Mir H, Wally MK, Seymour RB; Orthopaedic Trauma Association Musculoskeletal Pain Task Force. Clinical Practice Guidelines for Pain Management in Acute Musculoskeletal Injury. J Orthop Trauma. 2019 May;33(5):e158-e182. doi: 10.1097/BOT.0000000000001430. PubMed 30681429 ↗
  • Oyler DR, Slade E, Slavova S, Matuszewski PE, Lei F, Herndon B, Johnson S, Moghadamian ES. Effect of a Multimodal Analgesic Protocol on Short-Term and Long-Term Opioid Use After Orthopaedic Trauma. J Orthop Trauma. 2022 Aug 1;36(8):326-331. doi: 10.1097/BOT.0000000000002346. Epub 2022 Jan 6. PubMed 34999625 ↗
  • Mir HR, Miller AN, Obremskey WT, Jahangir AA, Hsu JR. Confronting the Opioid Crisis: Practical Pain Management and Strategies: AOA 2018 Critical Issues Symposium. J Bone Joint Surg Am. 2019 Dec 4;101(23):e126. doi: 10.2106/JBJS.19.00285. PubMed 31800430 ↗
  • Castillo RC, Raja SN, Frey KP, Vallier HA, Tornetta P 3rd, Jaeblon T, Goff BJ, Gottschalk A, Scharfstein DO, O'Toole RV; METRC. Improving Pain Management and Long-Term Outcomes Following High-Energy Orthopaedic Trauma (Pain Study). J Orthop Trauma. 2017 Apr;31 Suppl 1:S71-S77. doi: 10.1097/BOT.0000000000000793. PubMed 28323806 ↗
  • Marquez-Lara A, Hutchinson ID, Nunez F Jr, Smith TL, Miller AN. Nonsteroidal Anti-Inflammatory Drugs and Bone-Healing: A Systematic Review of Research Quality. JBJS Rev. 2016 Mar 15;4(3):e4. doi: 10.2106/JBJS.RVW.O.00055. PubMed 27500434 ↗
  • Cepeda MS, Carr DB, Miranda N, Diaz A, Silva C, Morales O. Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial. Anesthesiology. 2005 Dec;103(6):1225-32. doi: 10.1097/00000542-200512000-00018. PubMed 16306736 ↗
  • McDonald EL, Daniel JN, Rogero RG, Shakked RJ, Nicholson K, Pedowitz DI, Raikin SM, Bilolikar V, Winters BS. How Does Perioperative Ketorolac Affect Opioid Consumption and Pain Management After Ankle Fracture Surgery? Clin Orthop Relat Res. 2020 Jan;478(1):144-151. doi: 10.1097/CORR.0000000000000978. PubMed 31567579 ↗
  • Vadivelu N, Gowda AM, Urman RD, Jolly S, Kodumudi V, Maria M, Taylor R Jr, Pergolizzi JV Jr. Ketorolac tromethamine - routes and clinical implications. Pain Pract. 2015 Feb;15(2):175-93. doi: 10.1111/papr.12198. Epub 2014 Apr 16. PubMed 24738596 ↗
  • Brown CR, Mazzulla JP, Mok MS, Nussdorf RT, Rubin PD, Schwesinger WH. Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major surgery. Pharmacotherapy. 1990;10(6 ( Pt 2)):45S-50S. PubMed 2082313 ↗
  • Camu F, Van Overberge L, Bullingham R, Lloyd J. Hemodynamic effects of two intravenous doses of ketorolac tromethamine compared with morphine. Pharmacotherapy. 1990;10(6 ( Pt 2)):122S-126S. PubMed 2082308 ↗
  • De Oliveira GS Jr, Agarwal D, Benzon HT. Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. Anesth Analg. 2012 Feb;114(2):424-33. doi: 10.1213/ANE.0b013e3182334d68. Epub 2011 Sep 29. PubMed 21965355 ↗
  • Jelinek GA. Ketorolac versus morphine for severe pain. Ketorolac is more effective, cheaper, and has fewer side effects. BMJ. 2000 Nov 18;321(7271):1236-7. doi: 10.1136/bmj.321.7271.1236. No abstract available. PubMed 11082068 ↗
  • Gobble RM, Hoang HLT, Kachniarz B, Orgill DP. Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials. Plast Reconstr Surg. 2014 Mar;133(3):741-755. doi: 10.1097/01.prs.0000438459.60474.b5. PubMed 24572864 ↗
  • Irizarry E, Restivo A, Salama M, Davitt M, Feliciano C, Cortijo-Brown A, Friedman BW. A randomized controlled trial of ibuprofen versus ketorolac versus diclofenac for acute, nonradicular low back pain. Acad Emerg Med. 2021 Nov;28(11):1228-1235. doi: 10.1111/acem.14321. Epub 2021 Jun 30. PubMed 34133820 ↗
  • Motov S, Yasavolian M, Likourezos A, Pushkar I, Hossain R, Drapkin J, Cohen V, Filk N, Smith A, Huang F, Rockoff B, Homel P, Fromm C. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017 Aug;70(2):177-184. doi: 10.1016/j.annemergmed.2016.10.014. Epub 2016 Dec 16. PubMed 27993418 ↗
  • Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs. 1997 Jan;53(1):139-88. doi: 10.2165/00003495-199753010-00012. PubMed 9010653 ↗
  • Kinsella J, Moffat AC, Patrick JA, Prentice JW, McArdle CS, Kenny GN. Ketorolac trometamol for postoperative analgesia after orthopaedic surgery. Br J Anaesth. 1992 Jul;69(1):19-22. doi: 10.1093/bja/69.1.19. PubMed 1303630 ↗
  • Reinhart DI. Minimising the adverse effects of ketorolac. Drug Saf. 2000 Jun;22(6):487-97. doi: 10.2165/00002018-200022060-00007. PubMed 10877042 ↗
  • Lavoie A, Moore L, LeSage N, Liberman M, Sampalis JS. The New Injury Severity Score: a more accurate predictor of in-hospital mortality than the Injury Severity Score. J Trauma. 2004 Jun;56(6):1312-20. doi: 10.1097/01.ta.0000075342.36072.ef. PubMed 15211142 ↗
  • Lavoie A, Moore L, LeSage N, Liberman M, Sampalis JS. The Injury Severity Score or the New Injury Severity Score for predicting intensive care unit admission and hospital length of stay? Injury. 2005 Apr;36(4):477-83. doi: 10.1016/j.injury.2004.09.039. Epub 2005 Jan 22. PubMed 15755427 ↗
  • Weisz RD, Fokin AA, Lerner V, Flynt A, Macias-Perez I, Pavliv L, Crawford M, Puente I. Intravenous Ibuprofen Reduces Opioid Consumption During the Initial 48 Hours After Injury in Orthopedic Trauma Patients. J Orthop Trauma. 2020 Jul;34(7):341-347. doi: 10.1097/BOT.0000000000001733. PubMed 31929374 ↗
  • Singla N, Rock A, Pavliv L. A multi-center, randomized, double-blind placebo-controlled trial of intravenous-ibuprofen (IV-ibuprofen) for treatment of pain in post-operative orthopedic adult patients. Pain Med. 2010 Aug;11(8):1284-93. doi: 10.1111/j.1526-4637.2010.00896.x. Epub 2010 Jun 30. PubMed 20609131 ↗
  • Southworth S, Peters J, Rock A, Pavliv L. A multicenter, randomized, double-blind, placebo-controlled trial of intravenous ibuprofen 400 and 800 mg every 6 hours in the management of postoperative pain. Clin Ther. 2009 Sep;31(9):1922-35. doi: 10.1016/j.clinthera.2009.08.026. PubMed 19843482 ↗
  • Zhou HS, Li TT, Pi Y, Wang TH, Liu F, Xiong LL. Analgesic Efficacy of Intravenous Ibuprofen in the Treatment of Postoperative Acute Pain: A Phase III Multicenter Randomized Placebo-ControlledDouble-Blind Clinical Trial. Pain Res Manag. 2023 Mar 7;2023:7768704. doi: 10.1155/2023/7768704. eCollection 2023. PubMed 36926379 ↗
  • Eberson CP, Pacicca DM, Ehrlich MG. The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patient. J Pediatr Orthop. 1999 Sep-Oct;19(5):688-92. PubMed 10488877 ↗
  • 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. PubMed 29691180 ↗
  • 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. PubMed 32745216 ↗
  • 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. PubMed 31414128 ↗
  • Archer KR, Castillo RC, Wegener ST, Abraham CM, Obremskey WT. Pain and satisfaction in hospitalized trauma patients: the importance of self-efficacy and psychological distress. J Trauma Acute Care Surg. 2012 Apr;72(4):1068-77. doi: 10.1097/TA.0b013e3182452df5. PubMed 22491629 ↗
  • Bot AG, Bekkers S, Arnstein PM, Smith RM, Ring D. Opioid use after fracture surgery correlates with pain intensity and satisfaction with pain relief. Clin Orthop Relat Res. 2014 Aug;472(8):2542-9. doi: 10.1007/s11999-014-3660-4. Epub 2014 Apr 29. PubMed 24777731 ↗
  • Nota SP, Spit SA, Voskuyl T, Bot AG, Hageman MG, Ring D. Opioid Use, Satisfaction, and Pain Intensity After Orthopedic Surgery. Psychosomatics. 2015 Sep-Oct;56(5):479-85. doi: 10.1016/j.psym.2014.09.003. Epub 2014 Sep 6. PubMed 25624183 ↗
  • Shah A, Hayes CJ, Martin BC. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017 Mar 17;66(10):265-269. doi: 10.15585/mmwr.mm6610a1. PubMed 28301454 ↗
  • 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. PubMed 25911660 ↗
  • 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. PubMed 30779727 ↗
  • 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. PubMed 16781066 ↗
  • von Oelreich E, Eriksson M, Brattstrom O, Sjolund KF, Discacciati A, Larsson E, Oldner A. Risk factors and outcomes of chronic opioid use following trauma. Br J Surg. 2020 Mar;107(4):413-421. doi: 10.1002/bjs.11507. Epub 2020 Feb 7. PubMed 32031251 ↗
  • Norman SB, Stein MB, Dimsdale JE, Hoyt DB. Pain in the aftermath of trauma is a risk factor for post-traumatic stress disorder. Psychol Med. 2008 Apr;38(4):533-42. doi: 10.1017/S0033291707001389. Epub 2007 Sep 10. PubMed 17825121 ↗
  • Oostinga D, Steverink JG, van Wijck AJM, Verlaan JJ. An understanding of bone pain: A narrative review. Bone. 2020 May;134:115272. doi: 10.1016/j.bone.2020.115272. Epub 2020 Feb 13. PubMed 32062002 ↗
  • Martin BC, Fan MY, Edlund MJ, Devries A, Braden JB, Sullivan MD. Long-term chronic opioid therapy discontinuation rates from the TROUP study. J Gen Intern Med. 2011 Dec;26(12):1450-7. doi: 10.1007/s11606-011-1771-0. Epub 2011 Jul 13. PubMed 21751058 ↗
  • Van Zee A. The promotion and marketing of oxycontin: commercial triumph, public health tragedy. Am J Public Health. 2009 Feb;99(2):221-7. doi: 10.2105/AJPH.2007.131714. Epub 2008 Sep 17. PubMed 18799767 ↗
  • White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg. 2005 Nov;101(5 Suppl):S5-S22. doi: 10.1213/01.ANE.0000177099.28914.A7. PubMed 16334489 ↗
  • Choban PS, Weireter LJ Jr, Maynes C. Obesity and increased mortality in blunt trauma. J Trauma. 1991 Sep;31(9):1253-7. doi: 10.1097/00005373-199109000-00009. PubMed 1920556 ↗
  • Roberts CS, Pape HC, Jones AL, Malkani AL, Rodriguez JL, Giannoudis PV. Damage control orthopaedics: evolving concepts in the treatment of patients who have sustained orthopaedic trauma. Instr Course Lect. 2005;54:447-62. PubMed 15948472 ↗
  • DeLong WG Jr, Born CT. Cytokines in patients with polytrauma. Clin Orthop Relat Res. 2004 May;(422):57-65. doi: 10.1097/01.blo.0000130840.64528.1e. PubMed 15187834 ↗
  • McKinley TO, Gaski GE, Vodovotz Y, Corona BT, Billiar TR. Diagnosis and Management of Polytraumatized Patients With Severe Extremity Trauma. J Orthop Trauma. 2018 Mar;32 Suppl 1:S1-S6. doi: 10.1097/BOT.0000000000001114. PubMed 29461394 ↗
  • Brochner AC, Toft P. Pathophysiology of the systemic inflammatory response after major accidental trauma. Scand J Trauma Resusc Emerg Med. 2009 Sep 15;17:43. doi: 10.1186/1757-7241-17-43. PubMed 19754938 ↗
  • Tsirigotis P, Chondropoulos S, Gkirkas K, Meletiadis J, Dimopoulou I. Balanced control of both hyper and hypo-inflammatory phases as a new treatment paradigm in sepsis. J Thorac Dis. 2016 May;8(5):E312-6. doi: 10.21037/jtd.2016.03.47. PubMed 27162689 ↗
  • Cuschieri J, Bulger E, Schaeffer V, Sakr S, Nathens AB, Hennessy L, Minei J, Moore EE, O'Keefe G, Sperry J, Remick D, Tompkins R, Maier RV; Inflammation and the Host Response to Injury Collaborative Research Program. Early elevation in random plasma IL-6 after severe injury is associated with development of organ failure. Shock. 2010 Oct;34(4):346-51. doi: 10.1097/SHK.0b013e3181d8e687. PubMed 20844410 ↗
  • 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. PubMed 18084824 ↗
  • Giannoudis PV, Smith RM, Perry SL, Windsor AJ, Dickson RA, Bellamy MC. Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis. Intensive Care Med. 2000 Aug;26(8):1076-81. doi: 10.1007/s001340051320. PubMed 11030163 ↗
  • Hildebrand F, Giannoudis PV, van Griensven M, Chawda M, Pape HC. Pathophysiologic changes and effects of hypothermia on outcome in elective surgery and trauma patients. Am J Surg. 2004 Mar;187(3):363-71. doi: 10.1016/j.amjsurg.2003.12.016. PubMed 15006564 ↗
  • Pape HC, Schmidt RE, Rice J, van Griensven M, das Gupta R, Krettek C, Tscherne H. Biochemical changes after trauma and skeletal surgery of the lower extremity: quantification of the operative burden. Crit Care Med. 2000 Oct;28(10):3441-8. doi: 10.1097/00003246-200010000-00012. PubMed 11057799 ↗
  • Vanzant EL, Lopez CM, Ozrazgat-Baslanti T, Ungaro R, Davis R, Cuenca AG, Gentile LF, Nacionales DC, Cuenca AL, Bihorac A, Leeuwenburgh C, Lanz J, Baker HV, McKinley B, Moldawer LL, Moore FA, Efron PA. Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma. J Trauma Acute Care Surg. 2014 Jan;76(1):21-9; discussion 29-30. doi: 10.1097/TA.0b013e3182ab1ab5. PubMed 24368353 ↗
  • Gaski GE, Metzger C, McCarroll T, Wessel R, Adler J, Cutshall A, Brown K, Vodovotz Y, Billiar TR, McKinley TO. Early Immunologic Response in Multiply Injured Patients With Orthopaedic Injuries Is Associated With Organ Dysfunction. J Orthop Trauma. 2019 May;33(5):220-228. doi: 10.1097/BOT.0000000000001437. PubMed 31008819 ↗
  • Stutz CM, O'Rear LD, O'Neill KR, Tamborski ME, Crosby CG, Devin CJ, Schoenecker JG. Coagulopathies in orthopaedics: links to inflammation and the potential of individualizing treatment strategies. J Orthop Trauma. 2013 Apr;27(4):236-41. doi: 10.1097/BOT.0b013e318269b782. PubMed 22874115 ↗
  • Adib-Conquy M, Cavaillon JM. Compensatory anti-inflammatory response syndrome. Thromb Haemost. 2009 Jan;101(1):36-47. PubMed 19132187 ↗
  • McKinley TO, Gaski GE, Zamora R, Shen L, Sun Q, Namas RA, Billiar TR, Vodovotz Y. Early dynamic orchestration of immunologic mediators identifies multiply injured patients who are tolerant or sensitive to hemorrhage. J Trauma Acute Care Surg. 2021 Mar 1;90(3):441-450. doi: 10.1097/TA.0000000000002998. PubMed 33093290 ↗
  • Waydhas C, Nast-Kolb D, Trupka A, Zettl R, Kick M, Wiesholler J, Schweiberer L, Jochum M. Posttraumatic inflammatory response, secondary operations, and late multiple organ failure. J Trauma. 1996 Apr;40(4):624-30; discussion 630-1. doi: 10.1097/00005373-199604000-00018. PubMed 8614044 ↗
  • Malik A, Kanneganti TD. Function and regulation of IL-1alpha in inflammatory diseases and cancer. Immunol Rev. 2018 Jan;281(1):124-137. doi: 10.1111/imr.12615. PubMed 29247991 ↗
  • Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018 Jan;281(1):8-27. doi: 10.1111/imr.12621. PubMed 29247995 ↗
  • Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. 2011 Apr 7;117(14):3720-32. doi: 10.1182/blood-2010-07-273417. Epub 2011 Feb 8. PubMed 21304099 ↗
  • Aneja A, Landy DC, Mittwede PN, Albano AY, Teasdall RJ, Isla A, Kavolus M. Inflammatory cytokines associated with outcomes in orthopedic trauma patients independent of New Injury Severity score: A pilot prospective cohort study. J Orthop Res. 2022 Jul;40(7):1555-1562. doi: 10.1002/jor.25183. Epub 2021 Nov 2. PubMed 34729810 ↗
  • Berg DJ, Zhang J, Lauricella DM, Moore SA. Il-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production. J Immunol. 2001 Feb 15;166(4):2674-80. doi: 10.4049/jimmunol.166.4.2674. PubMed 11160331 ↗
  • Harizi H, Gualde N. Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derived inflammatory mediators. Cell Mol Immunol. 2006 Aug;3(4):271-7. PubMed 16978535 ↗
  • Chu CH, Chen SH, Wang Q, Langenbach R, Li H, Zeldin D, Chen SL, Wang S, Gao H, Lu RB, Hong JS. PGE2 Inhibits IL-10 Production via EP2-Mediated beta-Arrestin Signaling in Neuroinflammatory Condition. Mol Neurobiol. 2015 Aug;52(1):587-600. doi: 10.1007/s12035-014-8889-0. Epub 2014 Sep 14. PubMed 25218510 ↗
  • Spruijt NE, Visser T, Leenen LP. A systematic review of randomized controlled trials exploring the effect of immunomodulative interventions on infection, organ failure, and mortality in trauma patients. Crit Care. 2010;14(4):R150. doi: 10.1186/cc9218. Epub 2010 Aug 5. PubMed 20687920 ↗
  • Dionne RA, Khan AA, Gordon SM. Analgesia and COX-2 inhibition. Clin Exp Rheumatol. 2001 Nov-Dec;19(6 Suppl 25):S63-70. PubMed 11695255 ↗
  • Xiang L, Lu S, Fuller W, Aneja A, Russell GV, Jones LB, Hester R. Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma. Am J Physiol Heart Circ Physiol. 2012 Jan 1;302(1):H340-8. doi: 10.1152/ajpheart.00439.2011. Epub 2011 Oct 14. PubMed 22003055 ↗
  • Xiang L, Hester RL, Fuller WL, Sebai ME, Mittwede PN, Jones EK, Aneja A, Russell GV. Orthopedic trauma-induced pulmonary injury in the obese Zucker rat. Microcirculation. 2010 Nov;17(8):650-9. doi: 10.1111/j.1549-8719.2010.00061.x. PubMed 21044219 ↗
  • Peirce RJ, Fragen RJ, Pemberton DM. Intravenous ketorolac tromethamine versus morphine sulfate in the treatment of immediate postoperative pain. Pharmacotherapy. 1990;10(6 ( Pt 2)):111S-115S. PubMed 2082306 ↗
  • Lichtenstein DA, Meziere GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol. Chest. 2008 Jul;134(1):117-25. doi: 10.1378/chest.07-2800. Epub 2008 Apr 10. PubMed 18403664 ↗
  • Malek R, Soufi S. Pulmonary Edema. 2023 Apr 7. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK557611/ PubMed 32491543 ↗
  • Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int. 2012 May;81(9):819-25. doi: 10.1038/ki.2011.339. Epub 2011 Oct 5. PubMed 21975865 ↗
  • Kobbe P, Vodovotz Y, Kaczorowski DJ, Billiar TR, Pape HC. The role of fracture-associated soft tissue injury in the induction of systemic inflammation and remote organ dysfunction after bilateral femur fracture. J Orthop Trauma. 2008 Jul;22(6):385-90. doi: 10.1097/BOT.0b013e318175dd88. PubMed 18594302 ↗
  • 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. PubMed 23159957 ↗
  • 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. PubMed 28526155 ↗
  • Rogero MM, Calder PC. Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids. Nutrients. 2018 Mar 30;10(4):432. doi: 10.3390/nu10040432. PubMed 29601492 ↗
  • 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. PubMed 26009819 ↗
  • 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. PubMed 25371118 ↗
  • 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. PubMed 22110166 ↗
  • Pape HC, Marcucio R, Humphrey C, Colnot C, Knobe M, Harvey EJ. Trauma-induced inflammation and fracture healing. J Orthop Trauma. 2010 Sep;24(9):522-5. doi: 10.1097/BOT.0b013e3181ed1361. PubMed 20736786 ↗
  • 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. PubMed 23395471 ↗
  • 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. PubMed 35404445 ↗
  • 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. PubMed 23218935 ↗
  • 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. PubMed 11289091 ↗
  • 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. PubMed 26028838 ↗
  • 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. PubMed 28468607 ↗
  • 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. PubMed 27546764 ↗
  • 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. PubMed 17652366 ↗
  • 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. PubMed 19895952 ↗
  • 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. PubMed 37466669 ↗
  • 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. PubMed 21483522 ↗
  • 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. PubMed 26584270 ↗
  • 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. PubMed 20552333 ↗
  • Foster JA, Kavolus MW, Landy DC, Pectol RW, Sneed CR, Kinchelow DL, Griffin JT, Hawk GS, 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 Sep 25. doi: 10.1097/BOT.0000000000002703. Online ahead of print. PubMed 37752630 ↗
  • 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. PubMed 38506517 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Feb 2019 to primary completion in Jun 2023, 51 months.

Results were first posted in Jun 2025, 1 year 11 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 12, 2018
First posted
Sep 14, 2018
StartActual
Feb 28, 2019
Primary completionActual
Jun 20, 2023
CompletionActual
Jun 20, 2023
Results first posted
Jun 5, 2025
Last update
Jun 5, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 5, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03671746
Lead sponsor
Arun Aneja
Responsible party
Arun Aneja (Assistant Professor of Orthopaedic Surgery Traumatology Division, University of Kentucky) — Sponsor-investigator
First posted
Sep 14, 2018
Start date
Feb 28, 2019
Primary completion
Jun 20, 2023
Completion
Jun 20, 2023
Results posted
Jun 5, 2025
Last update
Jun 5, 2025

Study contacts

Arun Aneja, MD
principal investigator · University of Kentucky

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Ketorolac

Other studies in this condition

Multiple Trauma →

Start the discussion