Melatonin and type of delirium: is there an association?

Elderly patients, admitted with a traumatic hip fracture, are at an increased
risk for developing a delirium. The exact mechanisms behind the pathophysiology
of delirium remain uncertain. The pineal gland hormone melatonin may play a
significant role, since it is associated with circadian rhythmicity and normal
sleep, which is often compromised in patients suffering from a delirium.
Furthermore, melatonin might have analgesic effects, which might influence
levels of pain post-operatively, another known risk factor for delirium. Only a
small number of studies examined the association between type of delirium and
melatonin levels, and the relation between melatonin levels and pain scores in
elderly patients with traumatic hip fractures. One study examined the
association between the type of delirium and 6-SMT (metabolite of melatonin) in
24-hour urine samples. A hyperactive delirium was associated with a decrease of
6-SMT, while a hypoactive delirium was associated with an increase. However,
when interpreting these results, the methodological shortcomings and small
number of included patient in each group should be taken into account. Several
intervention studies preventively prescribing melatonin orally have taken
place, and show conflicting results. If there is indeed an association between
the type of delirium and the level of melatonin, this could help in
distinguishing patients who might and might not respond to treatment with
melatonin in future trials.

With this study we want to examine the association between the type of delirium
and melatonin levels in elderly patients with a hip fracture. We hypothesize
that a hyperactive delirium is associated with lower levels of melatonin, and a
hypoactive delirium with relatively higher levels of melatonin, in both saliva
and urine. Furthermore, we hypothesize that participants who experience more
pain show lower melatonin levels.

Primary questions:
1) Is there a significant difference between the postoperative levels of
6-sulfatoxymelatonin (6-SMT, metabolite of melatonine) in 24 hour urine
samples, in elderly patients with traumatic hip fractures, with and without a
delirium?
2) Is there an association between type of post-operative delirium
(hyperactive, mixed, hypoactive) and postoperatieve 6-SMT levels in 24 hour
urine samples, in elderly patients with traumatic hip fractures?

Secondary objectives:
3) Is there an association between the level pain (measured with the Visual
Analogue Scale (VAS) and the need for painkillers) and postoperative 6-SMT in
24 hour urine samples, in elderly patients with hip fractures?

Single-center cross-sectional study.

Female patients are routinely provided with a urinary tract catheter
perioperatively, which we will use to collect the 24 hour urine samples in
female participants. Male patients however are not routinely provided with a
catheter. The 24 hour urine of male participants without a catheter will be
collected either through a urinal or, if the participant is incontinent, a
condom catheter. They will be added by the nursing staff.

Participants will be asked to collect another sample of 24 hour urine 6 weeks
later, and hand this sample over to the laboratory at the time of regular
post-operative follow-up consultation at the (orthopedic) surgeon.

Caregivers will be asked to fill in a short questionnaire about the
participant's cognition (IQCODE-N).

The other procedures that are relevant for the study are all part of the
routine assessment of elderly patients with a hip fracture in the
Elisabeth-TweeSteden hospital, and will not lead to any extra burden.

There is no risk associated with participation.

As patients with dementia are most at risk for developing a delirium, we
consider it essential to include them in this study. This ensures that the data
is representable. Taking into account the research question, it is also
inevitable to include patients with a delirium. Moreover, we think that the
total burden of participation is relatively low, also for vulnerable patients,
.