Conditions: Postoperative Inflammatory Response
Keywords: Bilateral total knee replacement cytokine desmosine
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 30
Healthy volunteers: no

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.

Detailed description:

Arms:
arm 1: Hydrocortisone 100 mg IV Q 8hrs x3 arm 2: Saline IV Q8hr x3

Interventions: intervention 1: Hydrocortisone intervention 2: Saline
Intervention descriptions: intervention 1: Prepared by pharmacy, 100 mg, IV, every 8 hours, 3 times intervention 2: Prepared by pharmacy same volume as study drug, IV, every 8 hours 3 times

Protocol document: