Systolic Blood Pressure Measurement in Critically-ill Patients

Background/Significance:

Hypotension is common and predicts worse outcomes. Arterial hypotension, defined as an
arterial systolic blood pressure (BP) less than 90 mmHg in adults, represents the hallmark
of critical illness. Accurate arterial BP measurement is essential to deliver effective
treatment, to guide resuscitation, and to assess interventions. Non-traumatic hypotension
has been documented in as many as 19% of Emergency Department (ED) patients and those
patients with hypotension have a 10-fold increased risk of sudden, unexpected in-hospital
death.(1) Early hypotension is associated with increased mortality in survivors of cardiac
arrest, stroke, and STEMI,(2-4) stressing the need for a tool to rapidly and accurately
identify BP trends in order to effectively direct resuscitative measures. Additionally,
Doppler waveforms may provide additional clues of impending hemodynamic deterioration before
overt hypotension or shock ensues.

Disadvantages of the current system - The current initial standard for BP measurements in
most hospitals is via an automated non-invasive BP device that uses oscillometric
technology. This method has numerous limitations including non-continuous monitoring,
missing or delays in identifying hypotensive episodes, inaccuracy or inability to measure BP
due to various reasons including inaccurate cuff size or severity of hypotension. In one
study, 34% of patients had a BP discrepancy of ≥ 20 mmHg with the oscillometric device
compared to intra-arterial BP monitoring due to incorrect cuff size.(5) Oscillometric
devices are sufficient for use in many clinical situations; however, notable exceptions
include patients that are severely hypertensive, hypotensive, with arrhythmias, after
trauma, and other critical clinical scenarios, whereby manual auscultatory BP measurement is
preferred.(6) Even in non-critically ill patients, validation data of oscillometric
measurements has been called into question.(7) The alternative to oscillometric devices is
an intra-arterial catheter. Although accurate, intra-arterial catheters are invasive,
technically difficult to insert, expensive, time-intensive, painful, and with risks
including bleeding, infection, and neurovascular injury. Current guidelines for management
of critically ill patients suggest intra-arterial BP measurement is preferred over automatic
oscillometric non-invasive BP measurement. Despite this, in a recent survey of intensivists,
73% used non-invasive BP measuring devices in hypotensive patients.(8) For the above
reasons, researchers have been investigating newer technology to replace the oscillometric
technology; examples include Doppler and photoplethysmographic devices.(9;10) Newer
technology- The research and application of Doppler technology for measuring BP is in its
infancy and has yet to be fully realized. The benefits of such a device would include an
accurate, non-invasive means to measure BP in critically-ill patients. Due the high-risk of
missing hypotension, the possibility exists to commercialize the prototype for broader
clinical use in non-critically ill patients as well. The accuracy of Doppler velocimetry is
one important advantage. In an animal study comparing three indirect BP measuring
instruments- a Doppler ultrasonic flowmeter, an oscillometric device, and a
photoplethysmograph- to direct arterial pressure in cats, the Doppler and
photoplethysmographic devices had the highest overall accuracy. (10) In clinical practice,
when the initial automatic oscillometric BP device is unable to obtain a measurement due to
hypotension, the manual Doppler technique is a common practice due to its reliability and
referenced in one study as the "gold standard".(11) However, accurate systolic BP
measurement is only one parameter of the device. The Doppler signal received from the
arterial flow through the vessel has incredible potential to identify strength of pulse and
other auditory queues. This has been well established in peripheral arterial disease, with
descriptive terms used such as monophasic, biphasic, or triphasic pulses identified by
Doppler. The novel device has the potential to identify a "sick" pulse as determined by
changes in the Doppler waveform prior to hypotension ensues, as often, hypotension is very
late in the course of the disease process. To date, there is no automatic
sphygmomanometer/Doppler apparatus available.

This project will provide data to further the development of a novel blood pressure
monitoring device that will enable non-invasive and near-continuous blood pressure
monitoring and other hemodynamic information on critically-ill patients. Data from healthy
volunteers using a standard 8MHz (fetal) Doppler probe have already been collected in a
companion protocol in place at the University of North Carolina at Charlotte (UNCC).

Research Strategy:

1. Significance Identification of shock states before overt clinical evidence of shock
(i.e., hypotension) is challenging. Determining whether Doppler-measured arterial
waveforms can serve as a useful marker to identify hemodynamic compromise before shock
ensues is unknown.

2. Approach Hypothesis: Doppler waveform patterns in critically-ill hypotensive patients
have a unique and identifiable pattern.

Objectives:

1. Doppler waveforms will be collected from the brachial arteries of critically-ill
patients that present to the ED with overt evidence of shock.

This pilot study will allow us to obtain Doppler measurements in critically-ill
patients for comparison to non-critically-ill patients collected previously in an
IRB-approved study conducted at UNCC by the Co-PI.

Doppler signal measurements will be obtained from 20 critically-ill patients with
evidence of shock (i.e., hypotension with SBP < 90) in Emergency Department at
Carolinas Medical Center. Eligible patients will be identified from the Code Sepsis
clinical protocol alert by PCL currently utilized for other departmental studies or by
direct report from the PI while working in the ED. Patients or a legally authorized
representative will be approached for informed consent. The 8MHz Doppler probe, (fetal
ultrasound probe), will be applied to the brachial artery, and the position adjusted
until an adequate signal has been obtained. Doppler wave form data will be collected
over the course of a few minutes. It is anticipated that the patients will experience
minimal to no discomfort throughout this process.

Expected technical difficulties and how we will overcome them: The technical
difficulties will include ensuring consistent measurements, as the data will be
collected by the investigators and clinical research staff.

2. Develop a computer algorithm that will distinguish "healthy" from "sick" Doppler
waveforms.

Waveform characteristics from the ED patients will be compared to previously collected
waveforms from normal volunteers. A computer algorithm will then be developed to identify
distinguishing features between these waveforms (independent of blood pressure). We will use
a similar power analysis as done by Holt et al.(11)

1. Algorithm Development: We will use MATLAB (The MathWorks, Inc) to analyze the Doppler
signals obtained from the hypotensive/shock patients and compare them to prior obtained
healthy patient data in order to identify unique wave characteristics of patients in
shock.

2. Filtering: Optimum filtering software will be designed and perfected by the PIs, as
required by the quantified audio piezo-electric signal, to determine most reliable and
accurate Doppler waveform.

Sample Size Calculation Previous studies have used a power analysis that determined 18
observation sets (a set being one intra-arterial BP measurement and one Doppler BP
measurement) to detect a difference of 10% (deemed clinically significant by investigators)
between intra-arterial and Doppler BP with a SD for difference of 7.8 mmHg and an alpha of
0.05 using a two-sided one-sample t-test.

A power analysis was not performed for this pilot study. A sample size of twenty adult
subjects (with Doppler recording during of < or = 5 minutes) was chosen to ensure sufficient
observations. Further statistical techniques to improve association will be implemented as
described in the initial prototype description.

Inclusion Criteria:

1. Age ≥ 18

2. Systolic Blood Pressure < 90 mmHg

3. Normotensive patients with SBP > or = 90 mmHg with suspected hypoperfusion/shock

Exclusion Criteria:

1. Patients < 18 years of age

2. Pregnant patients