Randomized Controlled Trial for Exparel Hip Fracture

Osteoporotic fragility fractures of the hip are common in the geriatric population, are
increasing in frequency, and represent a growing social and economic burden. Pain control
after surgical treatment is an area of growing interest, as improvement in post-injury pain
is often an important indication for surgical treatment of hip fractures.

Typically a mainstay of post-operative pain control, the use of opiates has come under
increasing scrutiny, as it has been shown to be associated with delirium, respiratory
depression, and even may even lead to addiction or abuse in the medically frail geriatric
population. These concerns have led to efforts to minimize the use of post-operative opiates
in hip fracture patients. In that context, a treatment that could reduce the necessity of
post-op narcotics while still improving pain control would be potentially valuable.

There has been growing interest in the use of long-acting local anesthetics for improving
pain control in orthopaedics, particularly in the elective total joint arthroplasty
population. Studies have shown that arthroplasty patients receiving long-acting local
anesthetics have decreased opiate requirements, reduced length of stay, and lower costs.
Although well-demonstrated in the elective arthroplasty population, the effects of
long-acting local anesthetics have yet to be demonstrated in the hip fracture population.
Given that these fractures frequently occur in medically frail patients with multiple
comorbidities, in whom post-operative confusion and delirium are relatively common, there is
the potential for treatments that decrease opiate requirements to demonstrate substantial
medical and economic benefits.

Exparel (liposomal bupivacaine) and long-acting local anesthetics have been used extensively
in hip replacement surgery and have not been shown to be associated with any increased risks.
In the case of patients with displaced femoral neck fractures treated with arthroplasty, the
surgical techniques are identical to those being used in this study. Exparel has also been
used in trauma surgery as well as foot and ankle surgery without any increased described
risks, although its use explicitly in hip fractures has not been published. However, the PI
has trained in other medical centers where Exparel is routinely used in hip fracture patients
without any identified increased risks or complications, but there is a paucity of data on
this subject, which is the rationale for this study.

The investigators hypothesize that in patients with osteoporotic fragility fractures of the
hip, patients receiving intraoperative long-acting local anesthetics will have decreased pain
and decreased post-operative opiate requirements, leading to less delirium and decreased
hospital resource utilization during their index hospitalization.

The goal is to conduct a multi-center prospective randomized control trial to determine if
liposomal bupivacaine is superior to standard of care by addressing the below separate but
related aims:

1. Determine the effectiveness of Exparel to reduce narcotic requirements and pain post
operatively after hip fracture treatment. Excess narcotic use in the elderly population
is associated with a host of complications often magnified by polypharmacy, including in
hospital delirium, increased length of stay, nausea, constipation, urinary retention,
respiratory depression and others. Decreasing narcotic usage in this group of patients
following hip fracture can possibly reduce such complications. Patients will receive
standard of care medical treatment and be randomized to intra-operative Exparel vs.
placebo injections. Opioid requirements, complications, pain score, and length of stay
will be assessed in the post-operative period. Hypothesis: The investigators hypothesize
that total morphine requirements and pain scores will be decreased in this group
following the administration of exparel in the geriatric hip fracture fracture
population.

2. Determine the effectiveness of Exparel to reduce delirium in post-operative hip fracture
patients. In hospital delirium in elderly patients is associated with poor outcomes,
including prolonged length of stay, poor participation in rehabilitation, and falls. Use
of a locally administered liposomal bupivacaine could decrease the need for additional
medications for pain control in addition to decreased mental stress for patients in this
unfamiliar situation, thus resulting in decreased episodes of delirium. The
investigators will assess delirium utilizing Confusion Assessment Method (CAM) scores in
the post-operative period at regularly scheduled intervals and compare average scores
between the treatment / standard of care group. Hypothesis: The investigators
hypothesize that total episodes of delirium will be decreased in the liposomal
bupivacaine group.

3. Determine if Exparel is cost-effective in hip fracture patients. The costs associated
with increased narcotic usage, prolonged stay, resources, and complications can be
significant. The use of liposomal bupivacaine may lead to decreased resource utilization
to care for hip fractures. The investigators will conduct an economic analysis
evaluating total inpatient hospitalization costs including costs associated with length
of stay, medication requirements, and resources associated with consultations and
diagnostic evaluations. These costs will be compared against the cost of Exparel
administration to evaluate the net cost effect of the intervention. Hypothesis: The
investigators hypothesize that the net cost of inpatient care will be decreased when
compared to standard of care.

Inclusion Criteria:

- Age 55 or older

- Sustaining either an OTA/AO type 31A or 31B fracture undergoing ORIF or
hemiarthroplasty

- Able to consent

- Isolated injury

Exclusion Criteria:

- OTA/AO 31B1 (Impacted/slightly displaced)

- Baseline dementia or cognitive deficit

- Inability to consent

- Chronic Opioid use

- End stage liver disease with Model for End-Stage Liver Disease (MELD) greater than 20.

- End stage renal disease as defined by patients requiring hemodialysis at least twice
weekly

- Polytrauma, defined as: concurrent upper or lower extremity fracture, pelvis fracture,
spine fracture, rib fractures, or facial fractures, Blunt chest or abdominal trauma
resulting in diagnosed organ injury, Head trauma resulting in intracranial bleed or
diagnosed concussion

- Allergy to amide-type local anesthetics

- Prisoners (unlikely to be accessible for follow-up)