Parabens Flocculation on the Anti Inflammatory Effects of Corticosteroid Injections for Total Knee Arthroplasty

Corticosteroid injections have been used to treat inflammatory conditions for many decades
(Storz 1973; Roszental, Zurakowski and Blazar 2008). In order to maximize the effectiveness
on the synovial tissue, the concentrated form of corticosteroids is typically mixed with an
anesthetic preparation. The corticosteroid suspension in a large volume of anesthetic can
then disperse throughout the entire joint more effectively, especially in larger joints such
as the knee (Centeno and Moore 1994). In addition, the anesthetic provides immediate relief
to the area and can help verify that the injected site was the source of pain (Cole and
Schumacher 2005). Typical preparations of anesthetic medications are sold in multi-use vials.
The anesthetic solution usually contains a paraben preservative, except in the single vials
used for spinal injections, because the use of paraben preservatives is contraindicated in
spinal injections (Centeno and Moore 1994).

Celestone and Kenalog are two corticosteroid products that are commonly used for
intra-articular injections. If co-administration of a local anesthetic is desired, the
suspension of Celestone or Kenalog is commonly mixed with 1% or 2% Lidocaine hydrochloride
from multi-use vials containing parabens in Orthopedic and Rheumatology clinics.

The orthopedic literature relating to injections rarely addresses the use of the anesthetic
commonly used in injections. Flocculation occurs significantly when parabens are present, but
the influence on the efficacy of the corticosteroid is unknown (Philipose et al. 2011; Hwang
et al. 2016). There is abundant evidence that flocculation occurs when steroids are mixed
with anesthetic solutions containing parabens however, the clinical significance of this
phenomenon has not been reported. (Skedros and Pitts 2008b; Andreson, Deodhar and O'Rourke
2005; Skedros and Pitts 2008; Lutt, O'Rouke and Deodhar 2007; Cole and Schumacher 2005).

Cole and Schumacher (2005) suggest that flocculation can result from a chemical
incompatibility between corticosteroid and other agents. Flocculation that occurs when
corticosteroid is mixed with an anesthetic containing parabens may reduce the
anti-inflammatory effect of the steroid. There are two possible mechanisms in which the
corticosteroid preparation may be less effective. Flocculation may cause the corticosteroid
to precipitate, thus reducing dispersal within the injected area (Centeno and Moore 1994).
Additionally, flocculation may result from corticosteroid bonding with another molecule (such
as methylparaben) within the anesthetic preparation, making it chemically less effective. The
purpose of this study is to identify whether corticosteroid use with anesthetics containing
parabens reduces clinical effectiveness relative to paraben-free preparations.

STUDY DESIGN:

OBJECTIVES:

The purpose of this study is to identify whether corticosteroid use with anesthetics
containing parabens reduces clinical effectiveness relative to para-free preparations.

Hypothesis Alternate: Flocculation due to lidocaine containing parabens decreases the
anti-inflammatory effects of corticosteroids when compared to paraben-free lidocaine.

Procedure:

The investigator will enroll up to 100 patients, both male and female, between the ages of
18-89. Once the patient has been consented, They will be randomized into group 1 or group 2.
The randomization is a 1 to 1 ratio. Subsequent follow-up via phone call will take place on
week 1, week 2, week 4, week 8, and week 16.

Group 1: These patients will receive a corticosteroid solution with lidocaine containing
parabens.

Group 2: These patients will receive corticosteroid solution with paraben free lidocaine.

Corticosteroid injections will be given with or without ore-aspiration of synovial fluid.
Patient will be in supine position with superior-lateral injection.

Material identification: Celestone soluspan or Kenalog 1% 50mL multiuse vials without
epinephrine, 1% 5mL lidocaine vials, 10mL syringes with 21mm x 1 ¼ inch needles, alcohol
swabs, exam gloves, betadine solution.

DATA COLLECTION:

The investigator will collect the patients age, sex, BMI, Medical history, along with the
WOMAC survey, which asks about the patients knee and activity level and VAS, pain sale (0-10)
0 being the lease amount of pain and 10 being the worst.

Inclusion Criteria:

- Diagnosis of symptomatic primary knee osteoarthritis according to the American
Rheumatism Association classification criteria for knee osteoarthritis, ability to
understand study protocol and agreement to participate

Exclusion Criteria:

- History of any knee injection in the past 6 months, History of more than 2 injections
in the knee under study, previous fracture or surgical procedure of knee under
investigation, any benign or malignant tumor in knee, chemotherapy, hemearthosis,
current infection in the affected limb.