Postoperative Inflammatory Response
Conditions
Keywords
Bilateral total knee replacement, cytokine, desmosine
Brief summary
Inflammation related to cytokine release is known to occur with surgery. The cytokine IL6, a major marker of inflammation is known to increase during total joint replacement surgery. IL6 has been found to be elevated postoperatively in patients with hip fractures and has been linked to mental status changes and possibly other complications. It is known to lead to shock and participate in the inflammatory state seen in sepsis. High levels have further been linked to postoperative fever, confusion, symptoms of depression, acute respiratory distress syndrome (ARDS) and fat embolism syndrome (FES). Previously the investigators found that low dose steroids given in two doses in the initial perioperative period decreased the amount of IL6 released compared to placebo, but this was not sustained past 24 hours. Desmosine is a stable breakdown product of elastin from lung tissue that can be measured in urine samples. It is considered to be a marker of lung injury and is found to be elevated in patients with ARDS, congestive obstructive pulmonary disease and FES. Previously, the investigators have found that urine desmosine levels rise with bilateral total knee replacement compared to unilateral total knee replacement indicating possible lung injury. Therefore the investigators hypothesize: Continued low dose steroids given three times over a 24 hour period will: 1. Significantly decrease peak IL6 cytokine release during bilateral total knee replacement and maintaining this reduction in IL6 beyond 24 hours. 2. Decrease urinary desmosine levels, and hence be protective of lung injury.
Interventions
DRUGHydrocortisone
Prepared by pharmacy, 100 mg, IV, every 8 hours, 3 times
DRUGSaline
Prepared by pharmacy same volume as study drug, IV, every 8 hours 3 times
Sponsors
Hospital for Special Surgery, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Patients scheduled for bilateral total knee replacement * Between 50-90 years of age
Exclusion criteria
* Patients on steroid therapy * Patients that require stress-dose steroid pre-operatively * Patients that smoke * Patients that are diabetic * Patients younger than 50 or older than 90 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Decrease in IL6 Level | 24 hours postoperative |
Secondary
| Measure | Time frame |
|---|---|
| Blood Glucose | 24 hours postoperative |
| Length of Hospital Stay | Length of hospital stay, an expected average of 5 days |
| Desmosine Level | 24 hours postoperative |
| Mortality | Length of hospital stay, an expected average of 5 days |
| Ability to Ambulate | 48 hours |
| In Hospital Infection Rate | Length of hospital stay, an expected average of 5 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Steroid Hydrocortisone 100 mg IV Q 8hrs x3
Hydrocortisone: Prepared by pharmacy, 100 mg, IV, every 8 hours, 3 times | 15 |
| Control Saline IV Q8hr x3
Saline: Prepared by pharmacy same volume as study drug, IV, every 8 hours 3 times | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Control | Total | Steroid |
|---|---|---|---|
| Age, Continuous | 71 years STANDARD_DEVIATION 9 | 67.5 years STANDARD_DEVIATION 8 | 64 years STANDARD_DEVIATION 7 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 15 participants | 30 participants | 15 participants |
| Sex: Female, Male Female | 6 Participants | 15 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 15 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Decrease in IL6 Level
Time frame: 24 hours postoperative
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Steroid | Decrease in IL6 Level | 359.4 pg/ml |
| Control | Decrease in IL6 Level | 381.6 pg/ml |
Secondary
Ability to Ambulate
Time frame: 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Steroid | Ability to Ambulate | 1 Participants |
| Control | Ability to Ambulate | 1 Participants |
Secondary
Blood Glucose
Time frame: 24 hours postoperative
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Steroid | Blood Glucose | 133 mg/dL | Standard Deviation 30 |
| Control | Blood Glucose | 102 mg/dL | Standard Deviation 17 |
Secondary
Desmosine Level
Time frame: 24 hours postoperative
Population: Data were not collected
| Arm | Measure | Value |
|---|---|---|
| Steroid | Desmosine Level | 0 |
| Control | Desmosine Level | 0 |
Secondary
In Hospital Infection Rate
Time frame: Length of hospital stay, an expected average of 5 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Steroid | In Hospital Infection Rate | 0 Participants |
| Control | In Hospital Infection Rate | 0 Participants |
Secondary
Length of Hospital Stay
Time frame: Length of hospital stay, an expected average of 5 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Steroid | Length of Hospital Stay | 5 days | Standard Deviation 0.9 |
| Control | Length of Hospital Stay | 5 days | Standard Deviation 0.8 |
Secondary
Mortality
Time frame: Length of hospital stay, an expected average of 5 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Steroid | Mortality | 0 Participants |
| Control | Mortality | 0 Participants |