Orthostatic related blood pressure changes in syncope patients in the emergency department

Orthostatic hypotension (OH), a sustained fall in blood pressure with standing,
is caused by an excessive drop in the cardiac output and/or by an inadequate
vasoconstriction mechanism. OH is associated with increased (cardiovascular)
morbidity and mortality. It is relatively common in the elderly population and
the prevalence increases with age and varies between the chosen populations. In
community-dwelling elderly the prevalence is 6-30%, while the prevalence is up
to 50% in nursing home residents.
Therefore adequate recognition of OH is crucial. According to the consensus
definition, OH is a sustained drop of the systolic blood pressure of at least
20 mmHg and/or of the diastolic blood pressure of at least 10 mmHg within 3
minutes of standing. Recently there has been a lot of discussion about the
adequacy of the consensus definition, while it is based on expert opinion and
intermittent sphygmomanometric blood pressure measurements. With the increasing
use of the noninvasive continuous blood pressure measurement (Nexfin) there is
a better understanding of the different orthostatic blood pressure recovery
patterns. However, there is no clear definition for these different orthostatic
blood pressure recovery patterns. The orthostatic blood pressure recovery
patterns that have been described, can be divided into *normal recovery*, *slow
recovery*, *no recovery*, *initial orthostatic hypotension*, *delayed
orthostatic hypotension* and *reflex syncope*.

Syncope is 1-2% of the reasons for referral to the emergency department (ED)
whereby in up to 28% OH is listed as the cause. Measurement of the orthostatic
blood pressure is, according to the syncope guideline, part of the initial
evaluation of syncope in the ED. There are different ways to measure
orthostatic blood pressure changes. In the daily practice, the active
lying-to-standing test is the most suitable test, as it corresponds with real
life situations, is simple to perform and requires minimal patient cooperation.
Next to the call for revision of the consensus definition, a more standardized
and precise orthostatic blood pressure measurement method is recommended to be
implemented in the guidelines. The orthostatic blood pressure measurement with
sphygmanometer is too imprecise, too infrequently repeated during standing and
there is a wide variation in the measurement procedures and interpretation to
measure orthostatic hypotension in a sufficiently reliable matter. Orthostatic
blood pressure measurement with Nexfin seems to be very suitable. It can
identify orthostatic hypotension, as well as different blood pressure recovery
patterns including initial orthostatic hypotension, a clinically unrecognized
cause of syncope.
The clinical relevance of these different blood pressure recovery patterns
still needs to be identified before it can be used as a standard diagnostic
tool in the ED.
Next to the orthostatic blood pressure recovery patterns, different types of
pathophysiological changes have been recognized in orthostatic hypotension,
respectively arteriolar, venous and mixed. In the arteriolar type it is mainly
an impaired vasocontrictive mechanism to stress, in the venous type there is an
excessive decrease in venous return that is reflected in a sharp fall in the
cardiac output and in the mixed type there is a combination of both. When
taking the orthostatic blood pressure recovery patterns and the
pathophysiological types into account, it is possible to come to a rational
treatment. There have been many studies describing the different orthostatic
blood pressure recovery patterns and linking them to symptoms and mortality,
but no intervention and follow up of these patterns has been done.
Investigation of orthostatic blood pressure changes is primarily done in the ED
in the evaluation of syncope patients. The evaluation of syncope patients in
the ED is challenging, because most patients are asymptomatic at the arrival to
the ED. The aim of the evaluation is to detect the mechanism and the cause of
syncope, to be able to give the patient an effective, preventive treatment and
to determine the direct and long-term prognostic risk. The European Society of
Cardiology (ESC) has issued a syncope guideline to achieve a more efficient
initial evaluation. According to the ESC guideline the initial evaluation of
syncope consists of careful history and physical examination, including
orthostatic blood pressure measurement and electrocardiogram. Without any
further investigations the attending physician can make a diagnoses based on
the initial evaluation in 50- 63% of the syncope patients. In 21% of the
syncope patients the diagnosis could be made after the initial evaluation
combined with an additional history by a syncope expert. The additional value
of Nexfin in the initial evaluation and work-up of the syncope patient in the
ED still needs to be investigated. We hypothesize that following the ESC
guidelines with the initial evaluation together with Nexfin orthostatic
measurement and careful history taking more (correct) diagnosis will be made.
We also hypothesize that in (pre-) syncope patients with an abnormal blood
pressure recovery pattern an improvement of the abnormal blood pressure
recovery pattern with a directed treatment will give a reduction of (pre-)
syncope recurrence and improvement in quality of life. In patients with (pre-)
syncope with a normal blood pressure recovery pattern we expect a reduction of
(pre-) syncope and an improvement in quality of life due to (non-) medical
advices and treatment. We expect that Nexfin will be of prognostic added value
in both the initial evaluation as the follow-up period. At the end of this
study we hope to develop a more standardized orthostatic blood pressure
measurement method that can be used in the ED.

The main objective of the study is to determine the diagnostic and prognostic
added value of careful history taking and Nexfin in the initial evaluation of
(pre-) syncope patients in the ED and the follow-up period.

The secondary objective is to determine the effectiveness of therapeutic
intervention in (pre-) syncope patients with and without abnormal blood
pressure recovery patterns regarding recurrence of (pre-) syncope and quality
of life.

The study is a prospective, single-center intervention study. The estimated
duration of the study is 2 years. The study will take place in the ED of the
university medical center Groningen(UMCG) and will include patients who are
referred to the ED due to pre-syncope and syncope. The one-year follow up will
take place at the syncope outpatient department, which is part of the internal
medicine outpatient department. There will be a randomization 1:1 in the ED
between patients who will get an additional Nexfin measurement and patients
without this additional measurement. The randomization is done to be able to
determine the additional diagnostic and prognostic value of Nexfin in the ED en
during follow-up. We chose the intention-to-treat approach, as we are not
applying a new treatment and it would be unethical to spare patients from
proven care.

The study consists of two phases. The first phase is the initial evaluation in
the ED, the second phase is the follow-up in the outpatient department. The
initial evaluation will be done twice, first by the attending physician and
then by the investigator. The follow-up at the outpatient department will be
part of standard care. Patients will be asked to fill in a quality of life
questionnaire (SF-12) at the beginning and end of the follow-up period. They
will also be asked to do a MMSE and fill in the Barthel Index at their first
outpatient department visit. Next to this they will be requested to keep up a
diary about their (pre-)syncope complaints during the follow-up year.

Orthostatic blood pressure measurement is part of the initial evaluation of
(pre-)syncope patients in the ED.The burden for the patient in the ED is the
additional history taking and physical examination. The follow-up
investigations and treatment at the syncope outpatient department are part of
standard care. The burden for the patient is the request to keep up a diary
about their (pre-) syncope complaints during one year, a quality of life
questionnaire (SF-12) will be taken at the beginning and end of the study and
once a MMSE and Barthel index will be performed (in patients of 60 years and
older). The patients receive standard care, but because they are participating
in a study, they are asked to have regular outpatient department visits during
1 year. This means that some patients have more outpatient department visits
than they would normally require.