Polytrauma
Conditions
Keywords
Inflammatory cytokine, inflammation, trauma, opioid
Brief 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.
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.
Interventions
DRUGKetorolac
Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization
DRUGSaline Solution
Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization
Sponsors
Arun Aneja
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Participant medical team will be blinded to the treatment or placebo intervention
Intervention model description
Compare the effectiveness of a NSAID to placebo in acute trauma setting.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients age 18 to 75 * New Injury Severity Score (NISS) \> 9, with musculoskeletal injury requiring surgical treatment
Exclusion criteria
* Patient age \< 18 or \> 75 * Patients who presented more than 24 hours after time of injury * Patients with contraindications 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 immunocompromised/immunosuppressed condition or acquired immunodeficiency syndrome (AIDS) * Patients with pre-existing comorbidities (e.g., coronary artery disease, myocardial infarction, chronic organ failure, chronic obstructive pulmonary disease, emphysema, asthma, etc.) * Patients with chronic use of steroids, 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of Hospital Stay | Up to 30 days | Duration of the hospital stay will be calculated from electronic health record |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient Pain Scores | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 | 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. |
| Change in Interleukin 1a | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 | 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. |
| Change in Interleukin 1b | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 | 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. |
| Change in Interleukin 6 | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 | 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. |
| Change in Interleukin 10 | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 | 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. |
| Morphine Milligram Equivalents in House | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 | The the morphine milligram equivalents (MME) will be recorded throughout the course of the hospital stay. These will be reported as daily totals. |
| Post Traumatic Complications | Up to 30 days | 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. |
| Mortality | Up to 30 days | The Incidence of death related to the initial trauma/traumatic complications will be recorded for the first 30 days. |
| Change in Inpatient Subjective Pain Reports | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 | 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. |
| Change in Outpatient Subjective Pain Reports | up to 365 days | 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. |
| Change in Prostaglandin E-2 | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 | 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 |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
No enrolled participants were excluded from the study before assignment to groups.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Without NSAID Polytrauma participants will receive standard of care in addition to saline solution according to standard ATLS and standard ICU routine medical care.
Saline Solution: Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization | 35 |
| Standard of Care With NSAID Participants in the group will receive Ketorolac in addition to standard of care for the standard ATLS or ICU routine medical care.
Ketorolac: Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization | 35 |
| Total | 70 |
Baseline characteristics
| Characteristic | Standard of Care Without NSAID | Standard of Care With NSAID | Total |
|---|---|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 16.2 | 39.5 years STANDARD_DEVIATION 17.2 | 39.8 years STANDARD_DEVIATION 16.6 |
| Body Mass Index (BMI) | 29.5 kg/m^2 STANDARD_DEVIATION 6.4 | 28.2 kg/m^2 STANDARD_DEVIATION 7.3 | 28.9 kg/m^2 STANDARD_DEVIATION 6.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 35 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| New Injury Severity Score (NISS) | 15.1 units on a scale STANDARD_DEVIATION 6.4 | 14.0 units on a scale STANDARD_DEVIATION 5.2 | 14.6 units on a scale STANDARD_DEVIATION 5.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 33 Participants | 66 Participants |
| Sex: Female, Male Female | 11 Participants | 14 Participants | 25 Participants |
| Sex: Female, Male Male | 24 Participants | 21 Participants | 45 Participants |
| Surgery Count | 1.4 number of surgeries STANDARD_DEVIATION 0.7 | 1.2 number of surgeries STANDARD_DEVIATION 0.6 | 1.3 number of surgeries STANDARD_DEVIATION 0.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 6 / 35 | 3 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
Length of Hospital Stay
Duration of the hospital stay will be calculated from electronic health record
Time frame: Up to 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Without NSAID | Length of Hospital Stay | 7 days |
| Standard of Care With NSAID | Length of Hospital Stay | 8 days |
Comparison: Sample size calculations were performed using Length of Stay (LOS) as this was the primary outcome. Using a significance level of 0.05 and assumed standard deviation of 1.5 days, a sample size of 42 patients/group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was planned for 56 patients/group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: =0.275ANOVA
Secondary
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
Population: Change in patient pain scores during the hospital stay was inadvertently entered twice (as outcomes #3: Change in Patient Pain Scores and #11: Change in Inpatient Subjective Pain Reports). These represent identical outcomes which was change in patient pain during the hospital stay. Please refer to outcome #3 for the corresponding data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care Without NSAID | Change in Inpatient Subjective Pain Reports | Day 0 (Enrollment) | 55.1 score on a scale | Standard Deviation 27.5 |
| Standard of Care Without NSAID | Change in Inpatient Subjective Pain Reports | Day 1 | 52.2 score on a scale | Standard Deviation 31.3 |
| Standard of Care Without NSAID | Change in Inpatient Subjective Pain Reports | Day 2 | 53.9 score on a scale | Standard Deviation 26.5 |
| Standard of Care Without NSAID | Change in Inpatient Subjective Pain Reports | Day 3 | 54.1 score on a scale | Standard Deviation 27.3 |
| Standard of Care Without NSAID | Change in Inpatient Subjective Pain Reports | Day 4 | 59.5 score on a scale | Standard Deviation 26.9 |
| Standard of Care Without NSAID | Change in Inpatient Subjective Pain Reports | Day 5 | 59.2 score on a scale | Standard Deviation 25.6 |
| Standard of Care With NSAID | Change in Inpatient Subjective Pain Reports | Day 4 | 43.3 score on a scale | Standard Deviation 24 |
| Standard of Care With NSAID | Change in Inpatient Subjective Pain Reports | Day 0 (Enrollment) | 68.2 score on a scale | Standard Deviation 24.4 |
| Standard of Care With NSAID | Change in Inpatient Subjective Pain Reports | Day 3 | 56.3 score on a scale | Standard Deviation 26 |
| Standard of Care With NSAID | Change in Inpatient Subjective Pain Reports | Day 1 | 42.7 score on a scale | Standard Deviation 25.6 |
| Standard of Care With NSAID | Change in Inpatient Subjective Pain Reports | Day 5 | 52.6 score on a scale | Standard Deviation 21.9 |
| Standard of Care With NSAID | Change in Inpatient Subjective Pain Reports | Day 2 | 47.4 score on a scale | Standard Deviation 27.7 |
Secondary
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
Population: The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Without NSAID | Change in Interleukin 10 | Day 3 | 0.65 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 10 | Day 0 (Enrollment) | 1.10 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 10 | Day 4 | 0.49 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 10 | Day 2 | 0.57 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 10 | Day 5 | 0.72 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 10 | Day 1 | 0.90 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 10 | Day 5 | 0.75 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 10 | Day 2 | 0.62 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 10 | Day 0 (Enrollment) | 1.11 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 10 | Day 3 | 0.64 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 10 | Day 4 | 0.59 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 10 | Day 1 | 0.76 pg/mL |
Comparison: Sample size calculations were performed regarding LOS as this was the primary outcome measure. Using a significance level of 0.05 and an assumed SD of 1.5 days, a sample size of 42 patients per group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was originally planned for 56 patients per group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: =0.043Mixed Models Analysis
Secondary
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
Population: The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Without NSAID | Change in Interleukin 1a | Day 1 | 112.7 fg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1a | Day 3 | 104.2 fg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1a | Day 0 (Enrollment) | 115.1 fg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1a | Day 4 | 150.2 fg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1a | Day 2 | 119.3 fg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1a | Day 5 | 101.9 fg/mL |
| Standard of Care With NSAID | Change in Interleukin 1a | Day 2 | 135.4 fg/mL |
| Standard of Care With NSAID | Change in Interleukin 1a | Day 0 (Enrollment) | 138.8 fg/mL |
| Standard of Care With NSAID | Change in Interleukin 1a | Day 1 | 122.6 fg/mL |
| Standard of Care With NSAID | Change in Interleukin 1a | Day 5 | 148.7 fg/mL |
| Standard of Care With NSAID | Change in Interleukin 1a | Day 3 | 135.0 fg/mL |
| Standard of Care With NSAID | Change in Interleukin 1a | Day 4 | 85.2 fg/mL |
Comparison: Sample size calculations were performed regarding LOS as this was the primary outcome measure. Using a significance level of 0.05 and an assumed SD of 1.5 days, a sample size of 42 patients per group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was originally planned for 56 patients per group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: =0.564Mixed Models Analysis
Secondary
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
Population: The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Without NSAID | Change in Interleukin 1b | Day 0 (Enrollment) | 0.119 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1b | Day 1 | 0.095 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1b | Day 2 | 0.084 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1b | Day 3 | 0.091 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1b | Day 4 | 0.064 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 1b | Day 5 | 0.056 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 1b | Day 4 | 0.166 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 1b | Day 0 (Enrollment) | 0.119 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 1b | Day 3 | 0.108 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 1b | Day 1 | 0.130 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 1b | Day 5 | 0.126 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 1b | Day 2 | 0.118 pg/mL |
Comparison: Sample size calculations were performed regarding LOS as this was the primary outcome measure. Using a significance level of 0.05 and an assumed SD of 1.5 days, a sample size of 42 patients per group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was originally planned for 56 patients per group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: =0.118Mixed Models Analysis
Secondary
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
Population: The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Without NSAID | Change in Interleukin 6 | Day 0 (Enrollment) | 21.5 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 6 | Day 1 | 21.2 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 6 | Day 2 | 16.3 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 6 | Day 3 | 12.9 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 6 | Day 4 | 7.9 pg/mL |
| Standard of Care Without NSAID | Change in Interleukin 6 | Day 5 | 10.5 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 6 | Day 4 | 10.5 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 6 | Day 0 (Enrollment) | 20.6 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 6 | Day 3 | 11.2 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 6 | Day 1 | 14.6 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 6 | Day 5 | 10.8 pg/mL |
| Standard of Care With NSAID | Change in Interleukin 6 | Day 2 | 11.9 pg/mL |
Comparison: Sample size calculations were performed regarding LOS as this was the primary outcome measure. Using a significance level of 0.05 and an assumed SD of 1.5 days, a sample size of 42 patients per group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was originally planned for 56 patients per group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: 0.215Mixed Models Analysis
Secondary
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
Population: Only nine patients completed the required follow-up, resulting in insufficient data to conduct meaningful statistical analysis or draw clinically relevant conclusions.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard of Care Without NSAID | Change in Outpatient Subjective Pain Reports | -22.7 units on a scale |
| Standard of Care With NSAID | Change in Outpatient Subjective Pain Reports | -16.7 units on a scale |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care Without NSAID | Change in Patient Pain Scores | Day 1 | 52.2 score on a scale | Standard Deviation 31.3 |
| Standard of Care Without NSAID | Change in Patient Pain Scores | Day 3 | 54.1 score on a scale | Standard Deviation 27.3 |
| Standard of Care Without NSAID | Change in Patient Pain Scores | Day 4 | 59.5 score on a scale | Standard Deviation 26.9 |
| Standard of Care Without NSAID | Change in Patient Pain Scores | Day 0 (Enrollment) | 55.1 score on a scale | Standard Deviation 27.5 |
| Standard of Care Without NSAID | Change in Patient Pain Scores | Day 5 | 59.2 score on a scale | Standard Deviation 25.6 |
| Standard of Care Without NSAID | Change in Patient Pain Scores | Day 2 | 53.9 score on a scale | Standard Deviation 26.5 |
| Standard of Care With NSAID | Change in Patient Pain Scores | Day 5 | 52.6 score on a scale | Standard Deviation 21.9 |
| Standard of Care With NSAID | Change in Patient Pain Scores | Day 0 (Enrollment) | 68.2 score on a scale | Standard Deviation 24.4 |
| Standard of Care With NSAID | Change in Patient Pain Scores | Day 1 | 42.7 score on a scale | Standard Deviation 25.6 |
| Standard of Care With NSAID | Change in Patient Pain Scores | Day 2 | 47.4 score on a scale | Standard Deviation 27.7 |
| Standard of Care With NSAID | Change in Patient Pain Scores | Day 4 | 43.3 score on a scale | Standard Deviation 24 |
| Standard of Care With NSAID | Change in Patient Pain Scores | Day 3 | 56.3 score on a scale | Standard Deviation 26 |
Comparison: Sample size calculations were performed regarding LOS as this was the primary outcome measure. Using a significance level of 0.05 and an assumed SD of 1.5 days, a sample size of 42 patients per group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was originally planned for 56 patients per group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: <0.05Mixed Models Analysis
Secondary
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
Population: The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Without NSAID | Change in Prostaglandin E-2 | Day 0 (Enrollment) | 352.2 pg/mL |
| Standard of Care Without NSAID | Change in Prostaglandin E-2 | Day 1 | 477.0 pg/mL |
| Standard of Care Without NSAID | Change in Prostaglandin E-2 | Day 2 | 345.8 pg/mL |
| Standard of Care Without NSAID | Change in Prostaglandin E-2 | Day 3 | 319.8 pg/mL |
| Standard of Care Without NSAID | Change in Prostaglandin E-2 | Day 4 | 347.6 pg/mL |
| Standard of Care Without NSAID | Change in Prostaglandin E-2 | Day 5 | 266.9 pg/mL |
| Standard of Care With NSAID | Change in Prostaglandin E-2 | Day 4 | 304.7 pg/mL |
| Standard of Care With NSAID | Change in Prostaglandin E-2 | Day 0 (Enrollment) | 448.3 pg/mL |
| Standard of Care With NSAID | Change in Prostaglandin E-2 | Day 3 | 371.3 pg/mL |
| Standard of Care With NSAID | Change in Prostaglandin E-2 | Day 1 | 375.8 pg/mL |
| Standard of Care With NSAID | Change in Prostaglandin E-2 | Day 5 | 322.3 pg/mL |
| Standard of Care With NSAID | Change in Prostaglandin E-2 | Day 2 | 356.6 pg/mL |
Comparison: Sample size calculations were performed regarding LOS as this was the primary outcome measure. Using a significance level of 0.05 and an assumed SD of 1.5 days, a sample size of 42 patients per group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was originally planned for 56 patients per group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: =0.617Mixed Models Analysis
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Without NSAID | Morphine Milligram Equivalents in House | Day 0 (Enrollment) | 82.5 morphine milligram equivalents |
| Standard of Care Without NSAID | Morphine Milligram Equivalents in House | Day 1 | 67.75 morphine milligram equivalents |
| Standard of Care Without NSAID | Morphine Milligram Equivalents in House | Day 2 | 62 morphine milligram equivalents |
| Standard of Care Without NSAID | Morphine Milligram Equivalents in House | Day 3 | 72 morphine milligram equivalents |
| Standard of Care Without NSAID | Morphine Milligram Equivalents in House | Day 4 | 60 morphine milligram equivalents |
| Standard of Care Without NSAID | Morphine Milligram Equivalents in House | Day 5 | 63.75 morphine milligram equivalents |
| Standard of Care With NSAID | Morphine Milligram Equivalents in House | Day 4 | 30 morphine milligram equivalents |
| Standard of Care With NSAID | Morphine Milligram Equivalents in House | Day 0 (Enrollment) | 86 morphine milligram equivalents |
| Standard of Care With NSAID | Morphine Milligram Equivalents in House | Day 3 | 38.25 morphine milligram equivalents |
| Standard of Care With NSAID | Morphine Milligram Equivalents in House | Day 1 | 48.75 morphine milligram equivalents |
| Standard of Care With NSAID | Morphine Milligram Equivalents in House | Day 5 | 30 morphine milligram equivalents |
| Standard of Care With NSAID | Morphine Milligram Equivalents in House | Day 2 | 53 morphine milligram equivalents |
Comparison: Sample size calculations were performed using LOS as this was the primary outcome. Using a significance level of 0.05 and an assumed standard deviation of 1.5 days, a sample size of 42 patients/group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was originally planned for 56 patients/group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: <0.05Mixed Models Analysis
Secondary
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
Population: Two participants were excluded from the secondary analysis, as blood samples were not able to be collected from these patients (n=68). Due to a transition in our institution's electronic medical record, one patient's chart could not be recovered, hence secondary clinical outcomes could not be collected for this patient.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care Without NSAID | Mortality | 0 Participants |
| Standard of Care With NSAID | Mortality | 0 Participants |
Comparison: Sample size calculations were performed regarding LOS as this was the primary outcome measure. Using a significance level of 0.05 and an assumed SD of 1.5 days, a sample size of 42 patients per group (84 total) would yield 80% power to detect a difference of 0.928 days in average LOS between groups. Allowing for a dropout rate of up to 25%, recruitment was originally planned for 56 patients per group. Power calculations were performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland).p-value: <0.05Mixed Models Analysis
Secondary
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
Population: Two participants were excluded from the secondary analysis, as blood samples were not able to be collected from these patients. Due to a transition in our institution's electronic medical record, one patient's chart could not be recovered, hence secondary clinical outcomes could not be collected for this patient (n=67).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care Without NSAID | Post Traumatic Complications | Pulmonary Complications | 4 Participants |
| Standard of Care Without NSAID | Post Traumatic Complications | Acute Kidney Injury (AKI) | 2 Participants |
| Standard of Care With NSAID | Post Traumatic Complications | Pulmonary Complications | 3 Participants |
| Standard of Care With NSAID | Post Traumatic Complications | Acute Kidney Injury (AKI) | 0 Participants |