Delirium in Elderly Patients with Trauma of the Hip

Annually, 18.000 hip fracture patients are presented at a Dutch Emergency
Department and admitted to the hospital. The incidence is 5-13/10.000
(men/women); as in other Western countries and rises quickly in patients > 55
years. The number of hip fractures is expected to rise in the near-future to a
40% increase. An important reason for this is the double aging phenomenon; the
number of seniors is rising and in this group the mean age is increasing.

Hip fractures are associated with pain, which is an indicator for increased
risk of complications. A significant related complication of a hip fracture in
the elderly is a delirium, developing in 25% of elderly patients with hip
fractures during the clinical course. For a large proportion of those patients,
the trigger for development of delirium reaches back to the preoperative/acute
phase where polypharmacy, including opioid use and inadequately treated severe
pain are key players. Delirium is associated with negative health consequences,
increased hospital stay, falls, higher mortality, decreased physical function
and cognition, loss of Health Related Quality of life (HRQol),
re-hospitalization, higher admittance to nursing home, increased risk of
dementia and higher societal costs. Delirium avoidance is preferred over
treatment and therefore it is important to focus on preventive interventions.
In the 2011 Dutch quality indicators report, IGZ made assessment of delirium
and its treatment a quality of care indicator of hospitals. In the USA, the
AHRQ advices standard screening and assessment of delirium in a National
Quality Measure Clearinghouse. As severe, untreated pain is associated with a
higher delirium risk, pain should be treated optimally in this vulnerable
patient group, as early as possible, as pre-operative pain levels are directly
related to occurrence of a delirium. Patients with higher post-operative pain
have an increased hospital stay, delayed ambulation and long-term functional
impairment.
In moderate and severe pain, the current national guideline for pharmacological
treatment of acute traumatic pain advises
systemic opioids as first choice and morphine as first line agent when longer
acting analgesics are required. Opioids are often combined with paracetamol and
NSAIDs. The elderly patient is a challenge in good pain treatment, because of
physiological age-related changes, different drug effects, distribution,
metabolism and elimination. Opioids can lead to hypotension, respiratory
depression, nausea/vomiting, urinary retention and sedation. These drugs are
often under dosed, pain treated insufficiently and drugs as opioids and NSAID's
have been associated with an increased delirium risk. A nerve block alleviates
this clinical issues.

An example of a frequently used nerve block in patients with hip fractures is a
Fascia Iliaca Compartment Block (FICB). In an FICB, local anesthetics are
injected underneath the pelvic fascia iliaca to block femoral, obturator and
lateral cutaneous nerves to provide anesthesia of hip, thigh and knee. The
injection site is distant from major nerves and blood vessels and risks are
minimal.
Perioperatively, an FICB decreases need for systemic analgesia after total hip
arthroplasty and decreases urinary retention compared to morphine. Case series
and historically controlled studies show a single-shot FICB is a rapid, safe
and easy procedure providing excellent analgesia, decreased opioid need and
little risk of complications in children and adults with femoral and hip
fractures. A blind single-shot FICB was superior to morphine and NSAIDs in
patients with femoral shaft and hip fractures. Delirium as outcome was reported
in 1 RCT; a decreased
delirium incidence after using repetitive, blind, single-shot FICBs. However,
this study was not performed in the acute setting and pethidine (with
deliriogenic properties) was used as comparison. 2 Case series described a
continuous FICB in hip fractures and reported good pain control, decreased
length of stay without infectious complications.
Overall study quality is limited due to methodological issues (no control
groups, randomization or concealed allocation, high risk of bias), single-shot
FICBs and lack of medical endpoints. A well conducted RCT can provide solid
data on possible clinical and healthcare efficiency benefits.

In our study an ultrasound guided continuous FICB placed <2 hours after ED
presentation will be investigated. Leaving a catheter in place in the
compartment beneath the fascia will provide a route to administer LA
continuously, until 2 days after surgery, without the need for repetitive
insertions.
This study will provide evidence with respect to the value of a continuous FICB
administered early in the clinical course, in the Emergency Department. There
is no evidence about effectivity in pain treatment and delirium prevention when
started early and continued through
the entire clinical course.

The DEPTHip Study aims to shed light on the question whether the use of a
continuous ultrasound-guided FICB employing catheter technique, administered in
the ED within 2 hours after presentation of an elderly patient with a hip
fracture, can decrease the incidence of delirium during the clinical course
(hospital admission) and the first three months after discharge from the
hospital. The study will be conducted according to applicable (inter)national
regulatory requirements (WMO, GCP, Declaration of Helsinki 2004).

HYPOTHESIS
Because pain is treated more consistently and more effective, sooner after
presentation, lacking adverse events associated with the use of systemic
analgesia and less other drugs are required, the hypothesis is, that this will
decrease the risk of developing delirium in an elderly patient with a hip
fracture during the clinical course.

RESEARCH QUESTION
Does the use of a continuous ultrasound-guided FICB administered in the ED,
compared to usual care with systemic analgesics, will reduce the risk of
developing delirium until three months after discharge from the hospital in
elderly patients with hip fractures?

This study is designed as a prospective, open, multi center, randomized
interventional trial at four different study sites: Meander Medical Center in
Amersfoort, TerGooi hospital in Hilversum and both locations of Amsterdam UMC
(location VUmc and location AMC). These are two STZ hospitals and two academic
hospitals. Besides these centers, patients have been included for a period of
time in the Slotervaart hospital, until this hospital was closed. Patients will
be allocated to continuous FICB or care as usual according to national
guidelines on a 1:1 ratio and followed up until 3 months after hospital
discharge.

Patients will be randomized and allocated to one of two pain treatment
strategies:

1. Intervention
Ultrasound-guided administration of a continuous FICB, employing catheter
technique, whereby the catheter will remain in place until two days after
surgery. By leaving the catheter, pain is treated continuously by titrating LA
in the complete per-operative period.
For description of the technique of administration and handling of the nerve
block, see chapter 5.1 of the study protocol.

2. Comparison; traditional care
In moderate and severe pain, the current national guideline for pharmacological
treatment of acute traumatic pain advises systemic opioids as first choice and
morphine as first line agent when longer acting analgesics are required. In
patients with hip fractures, intravenous opioids are often combined with
intravenous paracetamol. The 2011 NICE guideline about analgesia in hip
fracture patients advices paracetamol as first line agent and opioids if
paracetamol alone does not offer sufficient pain relief. During the stay in the
ED and in the hospital this is the standard analgesic regimen. Right before and
during surgery, a nerve block (FICB or femoral nerve block, with or without
application of a catheter, is frequently used as part of standard care.
Post-operative pain is treated by a combination of intravenous and oral opioids
and paracetamol.

Patients are treated with registered medication for pain which is administered
by a frequently used route of administration, only the timing of the procedure
is different than during daily clinical practice. All patients who participate
risk the occurrence of known side effects of the drugs allocated for, as
described in the Summary of Product Characteristics (SPC) and risks of the
procedure. The latter are deemed small according to evidence; low risk of
infection and toxicity. Risks of usual care are well known, due to the systemic
effects of the drugs used in daily clinical practice.
The benefit of participation is increased awareness of occurrence of delirium
as well as increased awareness of pain experienced by the patient.
In case delirium is prevented, complications can be decreased and health care
costs will be saved.