Immunomodulation, IL-1 Inhibition, and Postoperative Incisional Pain

• Quantify the total analgesic requirement during the 72 hours following surgery [ Time Frame: 72 hours following surgery ] [ Designated as safety issue: No ]
  All analgesic consumption will be recorded. Comparisons between the placebo and active drug groups will be made at the conclusion of the study.
• Post-operative pain response will be measured [ Time Frame: 72 hours following surgery ] [ Designated as safety issue: No ]

  Pain will be measured at various time points in the 1st 72 hours following surgery by:

  1. Using a VAS scale at rest and with activity
  2. Mapping the area of hyperalgesia surrounding the surgical wound will using vonFrey's fibers
• Assess rates of wound infection [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
  Evaluation of the surgical wound for symptoms of wound infection will be made every day during hospitalization. Records from the first post-operative clinic visit will also be evaluated for evidence of wound infection.
• Assess rates of venous thrombosis [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
  Evaluation of the surgical wound for symptoms of venous thrombosis will be made every day during hospitalization. Records from the first post-operative clinic visit will also be evaluated for evidence of venous thrombosis.
• Assess rates of wound dehiscence [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
  Evaluation of the surgical wound for symptoms of wound dehiscence will be made every day during hospitalization. Records from the first post-operative clinic visit will also be evaluated for evidence of wound dehiscence.
• Total length of hospital stay [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  We will record total length of hospital stay for patients enrolled in the study.

The investigators hypothesize that perioperative administration of anakinra will reduce incisional pain by lowering the concentration of inflammatory mediators in surgical wounds. This knowledge is important because it suggests a new, previously unexplored pharmacological target for the control of postoperative incisional pain.

This study will test whether administration of anakinra, an IL-1 receptor antagonist, will decrease pain and improve wound healing in patients undergoing vascular or orthopedic surgical procedures. The investigators will administer two doses of Anakinra via an injection under the skin, one dose one hour before surgery and a second dose on the first postoperative day (24 hours after surgery). The investigators will remove fluid from the surgical incisions using a small plastic catheter placed under skin during surgery and measure the amounts of pain- causing inflammatory mediators. The investigators will also measure the amount of pain the participant is experiencing using questions about pain intensity and by gently touching the incision to determine sensitivity of the incision site.

• Pain
• Inflammation

• Drug: Anakinra
  An injection of Anakinra will be administered 1 hour prior to surgery and again 24 hours following surgery.
  Other Name: Kineret
• Drug: Normal Saline
  An injection of normal saline will be administered 1 hour prior to surgery and again 24 hours following surgery.

• Active Comparator: Anakinra
  Intervention: Drug: Anakinra
• Placebo Comparator: Saline injection
  Intervention: Drug: Normal Saline

Inclusion Criteria:

-Patients 18 years of age and older presenting to the Stanford Preoperative Evaluation Clinic prior to elective orthopedic surgical procedures or elective vascular surgical procedures not involving the abdominal aorta or carotid arteries.

Exclusion Criteria:

Patients will be excluded from participation if they have one or more of the following conditions:

1. Evidence of active local or systemic infection as demonstrated by fever, leukocytosis (white blood cell count > 11,000/ul), productive cough, new infiltrate on chest x-ray, or purulent drainage from any source
2. End-stage renal disease
3. A history of diabetic neuropathy
4. A malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the previous 5 years
5. Leukopenia (white blood cell count < 2,000/ul)
6. Thrombocytopenia (platelet count < 100,000/ul)
7. Abnormal liver function test result (aspartate aminotransferase or alanine aminotransferase level ≥1.5-fold the upper limit of normal)
8. A history or infection with tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
9. Pregnant or breastfeeding