• No results found

What You May Not Know

N/A
N/A
Protected

Academic year: 2021

Share "What You May Not Know"

Copied!
14
0
0

Loading.... (view fulltext now)

Full text

(1)

60 CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002

and mismanagement. The results of a recent pilot study1at 2 univer-sity-affiliated hospitals suggested a knowledge deficit in arterial pressure monitoring and some of the most basic aspects of hemo-dynamic monitoring. A total of 391 critical care nurses practicing in various critical care specialties were invited to participate in the study. The response rate was 17.4% (n = 68). Most of the partici-pants were between the ages of 30 and 39 years (56.1%) and had a baccalaureate degree as their basic (61.8%) and highest degree in nursing (58.8%). Most partici-pants had more than 4 years of nursing experience (94.1%) and critical care experience (83.9%), and most did direct ABP monitor-ing at least once or twice each week (97.1%). The participants were asked to complete an 18-item, criterion-referenced question-naire on ABP physiology, techni-cal aspects of ABP monitoring, and ABP waveform interpretation in selected pathophysiological conditions. The mean score in this pilot study was 36.7% (SD, 11.8%). Total scores ranged from 11.1% to 61.1%.

Literature on nurses’ knowl-edge of hemodynamic monitoring is limited, but several studies,2-5 Beate H. McGheeis an adult care

nurse practitioner and a recent graduate of the master’s program in the School of Nursing, University of Washington, Seattle, Wash. Maj Elizabeth J. Bridgeshas a doctoral degree from the School of Nursing, University of Washington, Seattle.

published and unpublished, indi-cate a general knowledge deficit in pulmonary artery pressure moni-toring. Because of these research findings, in this article, we focus on areas of particular knowledge deficit related to essential princi-ples of hemodynamic monitoring and ABP monitoring. We discuss the physiology of ABP, physiologi-cal and pathophysiologiphysiologi-cal factors that affect ABP, and the arterial pressure waveform and its inter-pretation in clinical situations common in critical care patients.

ABP PHYSIOLOGY

The cardiovascular system has 3 types of pressures6,7: hemody-namic, kinetic energy, and hydro-static. Hemodynamic pressure is the energy imparted to the blood by contraction of the left ventricle. This type of pressure is preserved by the elastic properties of the arterial system. Kinetic energy is the energy associated with motion and affects the pressure measured during direct ABP monitoring. Fluid density and gravity con-tribute to hydrostatic pressure, which is the pressure a column of fluid exerts on the container wall. For example, in a column of fluid, the pressure at a given level in the container is proportional to the

Monitoring Arterial

Blood Pressure:

What You May Not Know

Beate H. McGhee,

BSN, MN, APN

Maj Elizabeth J. Bridges,

USAF, NC

r t e r i a l blood pres-sure (ABP) is a basic h e m o d y -n a m i c index often utilized to guide therapeutic interventions, especially in critically ill patients. Inaccurate ABP measuring cre-ates a potential for misdiagnosis

A

To purchase reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints@aacn.org.

To receive CE credit for this article, visit the American Asso-ciation of Critical-C a r e N u r s e s ’ (AACN) Web site at http://www.aacn .org, click on "Education" and select “Continuing Education,” or call AACN’s Fax on Demand at (800) 222-6329 and request item No. 1152.

(2)

CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 61

height of the fluid column above that level. The pressure is highest at the bottom of the column. In the vascular system, hydrostatic pressure is proportional to the height of the column of blood between the heart and the periph-eral vasculature. In a standing person, the pressure in the leg is higher than the pressure in the arm by the difference in hydro-static pressure. In summary, arte-rial blood pressure represents the force exerted by the blood per unit area on the arterial wall6-8and is the sum of hemodynamic, kinetic, and hydrostatic pressure.

The arterial tree starts with the aorta and the major branches of this vessel. The aorta and its branches stretch to receive blood from the left ventricle and recoil to distribute the blood and to maintain arterial pressure. Art-eries and arterioles control blood pressure through vasoconstric-tion or vasodilavasoconstric-tion.6Arterioles are the primary sites that con-tribute to systemic vascular resis-tance (SVR).6,9-11 In addition, adrenergic control of the arteri-oles is a major determinant of blood flow into the capillaries. In the skin, for instance, blood can be shunted from the capillary beds to flow directly from arteri-oles into the venous system.9 Arteriovenous shunting occurs in shock states and helps to redirect blood flow to vital organs. Arterio-venous shunting is one reason measurements of blood pressure alone are not a good indicator of peripheral tissue perfusion.

Arterial pressure is measured at its peak, which is the systolic blood pressure (SBP), and at its trough, which is the diastolic blood pres-sure (DBP). The SBP is determined by the stroke volume, the velocity of left ventricular ejection (an

indi-rect indicator of left ventricular contractile force), systemic arterial resistance, the distensibility of the aortic and arterial walls, the vis-cosity of blood, and the left ven-tricular preload (end-diastolic volume).11-13The blood pressure in the aorta during systole is a clinical indicator of afterload (the sum of the forces the left ventricle must overcome to eject blood).14,15The diastolic pressure is affected by blood viscosity, arterial distensibil-ity, systemic resistance, and the length of the cardiac cycle.11,16

Pulse pressure is the difference between systolic and diastolic pressure. A normal pulse pressure in the brachial artery is approxi-mately 40 mm Hg. An increased pulse pressure may be the result of increased stroke volume or ejec-tion velocity and is common dur-ing fever, exercise, anemia, and hyperthyroidism.11Other causes of increased pulse pressure include bradycardia (increased stroke vol-ume), aortic regurgitation, and arterial stiffening, which is most noticeable after the age of 50 to 60 years.11,17-19An acute decrease in pulse pressure may indicate an increase in vascular resistance, decreased stroke volume, or decreased intravascular volume.11-13 Systemic mean arterial pres-sure (MAP) is defined as the mean perfusion pressure throughout the cardiac cycle. MAP is sensed by baroreceptors located in the carotid sinuses and the arch of the aorta. These receptors control arte-rial pressure mainly by adjusting heart rate and arteriolar vessel radius. MAP is also the basis for autoregulation by some organ sys-tems such as the kidney, heart, and brain. Autoregulation is the auto-matic adaptation of the radius of an arteriolar vessel in an organ to maintain constant blood flow over

a wide range of mean pressures (60-150 mm Hg) to protect func-tioning of the organ.7,20MAP is the product of SVR and cardiac output (MAP=SVR×cardiac output).7,10

As indicated previously, a main determinant of SVR is the radius of arterial, and particularly arteriolar, vessels. Changes in cardiac output are related to heart rate and stroke volume. Stroke volume, in turn, is determined by several factors, including heart rate, preload, after-load, cardiac contractility, and syn-ergy of cardiac contraction (related to ventricular dilatation, abnormal-ities in ventricular wall motion, and ventricular arrhythmias).10,11MAP is generally closer to diastolic pres-sure because diastole represents about two thirds of the cardiac cycle when the mean heart rate is close to 60/min. This relationship is expressed in the well-known for-mulas MAP = DBP + (SBP -DBP)/3 and MAP = [SBP + (DBP x 2)]/3.

However, the proportion of diastole in the cardiac cycle changes with changes in heart rate. In calculations of MAP for a manually obtained ABP, these for-mulas must be used with caution, because they provide a good esti-mate of MAP only when the heart rate is close to 60/min.10 Fortu-nately, MAP is provided by most automatic ABP measuring devices and direct ABP monitoring sys-tems, each of which uses a system-specific method to directly determine MAP.

In summary, because of the multiplicity of factors that con-tribute to ABP and the complexity of their interrelationships, inter-preting changes in arterial pres-sure and its components (SBP, DBP, MAP, and pulse pressure) as indicative of any single factor may lead to an erroneous assessment of a patient’s condition. When SBP

(3)

62 CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 and DBP are measured using

dif-ferent (oscillometric or direct) monitoring methods, the values can differ significantly. When MAP is measured using different moni-toring methods, however, the val-ues are very similar, because MAP is little affected by the phenom-enon of wave reflection.21-25Wave reflection and other factors that affect measurement of SBP and DBP are discussed later.

PRINCIPLES OF

HEMODYNAMIC

MONITORING

Three Conventions of

Cardiovascular Pressure

Measurement

For measurement of cardio-vascular pressures, 3 conventions are observed6,7,20: (1) Cardio-vascular pressures are expressed in millimeters of mercury, with the exception of central venous pressure, which may be measured in millimeters of mercury or in centimeters of water. For convert-ing values in centimeters of water to values in millimeters of mer-cury, the value given in centime-ters of water is divided by the factor 1.36. (2) Most cardiovascu-lar pressures, such as ABP, central venous pressure, and pulmonary artery pressure, are referenced to the heart or, more specifically, to the atria, to eliminate hydrostatic pressure. (3) All cardiovascular pressure monitoring devices are zeroed to ambient atmospheric pressure, so that the actual sure measured reflects the pres-sure above atmospheric prespres-sure.

The Hemodynamic

Monitoring System

A hemodynamic monitoring system contains 2 compartments: the electronic system and the fluid-filled tubing system.

Al-though clinicians have little con-trol over the electronic compo-nents such as the monitor, correct setup and maintenance of the tubing system and the pressure transducer are absolutely crucial to avoid error. With an improperly prepared or inadequately func-tioning monitoring system, not only the actively measured hemo-dynamic indices but also any derived variables will be errone-ous,26potentially invalidating a patient’s entire hemodynamic pro-file. Three procedural steps should be followed to prepare the moni-toring tubing system and ensure its continued accuracy: priming of the pressure tubing, leveling and zero-ing, and dynamic response testing.

Priming of the Pressure Tubing.

The generation and recording of all arterial waveforms (systemic arteri-al pressure and pulmonary artery pressure) are based on the same basic principles. The invasive catheter provides access to the arterial system being monitored and is designed to pick up the pres-sure waves generated in the arterial system by cardiac contractions. The catheter is connected to the fluid-filled tubing of the monitor-ing system. The fluid column in the tubing system carries the mechan-ical signal created by the pressure wave to the diaphragm of the elec-trical pressure transducer. The transducer creates the link between the fluid-filled tubing system and the electronic system, and converts the mechanical signal into an elec-trical signal. The elecelec-trical signal is transmitted to the monitor and then is amplified and displayed as an analog waveform and digital output.

Air as a medium transmits mechanical impulses much dif-ferently than does fluid. Air bub-bles in the tubing system are one

of the most frequent and impor-tant sources of error in hemody-namic monitoring. Air bubbles most often blunt or damp propa-gation of the mechanical signal, causing a damped analog wave-form and erroneous pressure readings.27Even tiny air bubbles only 1 mm in diameter can cause serious waveform distortion.28 Therefore, air-free priming of the entire tubing system is one of the most important steps to avoid technical error.

Air-free priming starts with removal of all air from the flush solution to prevent air from going into the solution as a result of the pressure applied by the external pressure cuff. Then, the entire tubing system should be flushed. Stopcocks, Luer-Lok interconnec-tions, and the transducer are com-mon locations of air entrapment27 and deserve special attention throughout priming and use of the catheter system. In order to main-tain the air-free status after the initial setup of the system, the fol-lowing measures are important:

■After opening the system for blood sampling or zeroing, briefly fast-flush the tubing system, including the proximal access stopcock or the air-fluid interface stopcock.

■Tighten all connections, and ensure that the stopcocks are closed to air.

■Avoid adding stopcocks and line extensions.

■Keep the flush solution bag adequately filled, and keep the external pressure cuff at 300 mm Hg. ■Periodically flick the tubing system and flush the tubing sys-tem and stopcocks to eliminate tiny air bubbles escaping the flushing solution.

Leveling and Zeroing. The

(4)

sys-tem must be referenced to heart level, technically the level of the left atrium, and set at atmospher-ic pressure as the zero reference point. These criteria can be met through leveling and zeroing. Leveling or referencing of the catheter system is accomplished by aligning the air-fluid interface of the monitoring system (eg, the stopcock on top of the transduc-er) with the external reference point of the heart. The external reference point of the heart is the phlebostatic axis, which can be located by finding the junction of 2 lines: a vertical line drawn out from the fourth intercostal space at the sternum and a horizontal line drawn through the midpoint of a line going from the anterior to the posterior side of the chest.29,30

Where to level the air-fluid interface is a matter of discussion. The answer depends on which vascular bed is to be monitored. In most clinical situations, the

central arterial pressure is the pressure of interest, because it is a key determinant in cardiac and cerebral perfusion. In order to monitor central arterial pressure, the monitoring system must be leveled to the heart by using the phlebostatic axis. Research indi-cates that the phlebostatic axis most accurately reflects the level of the atrium in both supine and upright patients.29-31 The midaxil-lary line, which has also been used as an external reference point for the heart, is not accurate in all chest configurations and thus is not recommended.31When the monitoring system is refer-enced to the tip of the catheter, then the transmural pressure of a particular point in the arterial tree is monitored and not central arte-rial pressure. Peripherally mea-sured transmural pressure is markedly increased by hydrostat-ic pressure unless the patient is supine.32

Zeroing consists of 2 steps. First, the air-fluid interface is opened to atmospheric pressure. Then the monitor’s zeroing func-tion key or button is pressed. Zeroing in this fashion has several purposes. Zeroing electronically establishes for the monitor atmo-spheric pressure as the atmospher-ic zero reference point. Zeroing establishes the interface level as the hydrostatic zero reference point. Zeroing also eliminates zero-drift. Zero-drift is the potential, but usually minimal, transducer offset or distortion occurring over time.33

Two key practice objectives are related to referencing and zeroing: accuracy and consistency. In order to ensure accuracy, leveling and zeroing must be done whenever the relationship between the air-fluid interface and the reference point is changed. The reason is hydrostatic pressure. For every 1 cm the air-fluid interface is above or below the actual level of the left

(5)

atrium, 0.74 mm Hg of hydrostatic pressure is subtracted or added to the measured pressure. If the air-fluid interface is placed 10 cm below the phlebostatic axis, the measured pressure will be an over-estimation of the actual hemody-namic pressure by 7.4 mm Hg. This example illustrates that though accurate referencing and zeroing are important for all hemodynamic monitoring, they become even more crucial when small hemody-namic pressures, such as pul-monary artery wedge pressure (6-12 mm Hg) and central venous pressure (2-6 mm Hg) are being monitored. In these instances, small offsets from the phlebostatic axis and the zero reference point can cause large errors34and may prompt inappropriate treatment.

In order to ensure consistency, once the external reference point has been selected, it should be marked on the patient for easy identification. Consistency allows

correct determination of trends in a patient’s hemodynamic status. Whether the same body position must be used for consecutive measurements may be debatable. Although several studies on pul-monary artery pressure monitor-ing indicated no significant changes in pulmonary artery pressures related to certain bed positions, according to a recent research abstract,35ABP values obtained with various bed posi-tions differed even when the phle-bostatic axis was used as the external reference point. The sta-tistical significance of differences in ABP values for monitoring sys-tems referenced to the phlebo-static axis was not addressed in the abstract.

Dynamic Response Testing. In

order to determine if a hemody-namic monitoring system can adequately reproduce a patient’s cardiovascular pressures, the dynamic response characteristics

of the catheter system must be tested. Only when system accura-cy, also termed fidelity, has been confirmed, can the analog wave-form be accepted as an accurate reflection of a patient’s status.

The dynamic response of a hemodynamic monitoring system is defined by its natural frequency and the damping coefficient. The natural frequency indicates how fast the pressure monitoring sys-tem vibrates when shock excited by a signal such as the arterial pres-sure pulse or the prespres-sure signal caused by a fast-flush test. The damping coefficient of a monitor-ing system is a measure of how quickly the oscillations of a shock-excited system dampen and even-tually come to rest.23,26,36

Dynamic response testing is a 3-step procedure: determining natural frequency, determining the amplitude ratio of 2 consecu-tive fast-flush oscillations (as an indirect way of determining the

(6)

CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 67

damping coefficient), and deter-mining the dynamic response characteristics of the monitoring system (eg, optimal, adequate, underdamped, overdamped, or unacceptable). These steps are summarized in Figure 1.

Dynamic response testing may seem complicated at first. Clinical experience has shown, however, that with proper training, dynam-ic response testing can be per-formed in less than 2 minutes. A few simple observations provide almost as much information and may serve as a close estimate. (1) If the period between 2 oscilla-tions of the fast-flush test is less than 1.2 mm, then natural fre-quency will be at least 21, and the system will most likely be ade-quate. If the period between 2 oscillations is 1 mm or less, then the natural frequency is 25 or higher, and the system will almost always function properly with any degree of damping. As a rule-of-thumb, the higher the natural fre-quency (or the smaller the period), the better is the dynamic response of the monitoring sys-tem. (2) The system is over-damped if the fast-flush produces sluggish or no oscillations. If the square wave shows undulations or if ringing occurs after the release of the fast-flush device, the system is most likely damped. Overdamping and under-damping both indicate that the dynamic response characteristics of the monitoring system are unsatisfactory.

Simple visual evaluation of the arterial waveform, the square waveform, and oscillations gener-ated by the fast-flush has been suggested as a suitable method for determining the dynamic response characteristics of a monitoring system. However, the

square waveform and fast-flush oscillations may look adequate when the natural frequency and amplitude ratio of the system actually make the system inade-quate (underdamped, over-damped, or unacceptable). Or, the arterial waveform may look dis-torted because of physiological variations, yet the dynamic re-sponse characteristics of the sys-tem assure a faithful recording of the arterial pressure.36When accu-racy is needed for clinical decision making, the ideal method of deter-mining if the measured ABP, or any other directly monitored hemodynamic parameter, is true is to determine the dynamic re-sponse characteristics of the moni-toring system.26,36Examples of the importance of formally assessing the response characteristics are discussed in more detail later.

COMPONENTS OF

THE NORMAL ABP

WAVEFORM

Left ventricular contraction creates a pressure pulse or pulse wave. It is the pressure pulse that a clinician feels when determin-ing a patient’s pulse by palpation. The pressure pulse is also what is sensed by the intra-arterial catheter.34,35The normal arterial pressure waveform is shown in Figure 2. The systolic upstroke or anacrotic limb mainly reflects the pressure pulse produced by left ventricular contraction. The pres-sure pulse is followed slightly later by the flow wave caused by the actual displacement of blood volume. The anacrotic shoulder, that is, the rounded part at the top of the waveform, reflects primari-ly volume displacement.22,37The systolic pressure is measured at the peak of the waveform. The dicrotic (or downward) limb is

demarcated by the dicrotic notch, representing closure of the aortic valve and subsequent retrograde flow. The location of the dicrotic notch varies according to the tim-ing of aortic closure in the cardiac cycle. For example, aortic closure is delayed in patients with hypov-olemia. Consequently, the dicrot-ic notch occurs farther down on the dicrotic limb in hypovolemic patients. The dicrotic notch also appears lower on the dicrotic limb when arterial pressure is measured at more distal sites in the arterial tree (Figure 3). The shape and proportion of the dias-tolic runoff wave that follows the dicrotic notch changes with arte-rial compliance and heart rate. Diastolic pressure is measured just before the beginning of the next systolic upstroke.

The analog waveform visible on the monitor or recorded on a strip chart is not only caused by the forward pressure pulse but is also a result of a phenomenon known as wave reflection. Wave reflection is related to the im-pedance of blood flow by the nar-rowing and bifurcation of the arterial vessels; the impedance leads to backward or retrograde reflection of the pressure wave.23,38-40 In a manner similar to waves on the beach, the forward or ante-grade pressure waves and the reflected waves collide. The com-bination of the 2 types of waves increasingly augments the SBP the farther down the blood pres-sure is meapres-sured in the arterial circuit. In other words, the contri-bution of reflected waves to the measured systolic pressure occurs earlier in the periphery, particu-larly in the radial and dorsalis pedis arteries (Figure 3), where the measured SBP may be 20 to 25 mm Hg higher than central aortic

(7)

68 CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 1. Determining natural frequency (Fn)

At the end of a waveform

a. Perform the fast-flush maneuver (square waveform test): pull and release the pigtail or compress and release the button of the fast-flush device of the monitoring system.

b. Record the resulting square waveform and subsequent oscillations on calibrated strip chart paper. c. Measure the distance (period, t, of 1 cycle) in millimeters between 2 oscillations. (One small box on the

calibrated strip chart paper equals 1 mm.) d. Calculate Fn by using the formula

Fn = paper speed (mm/s)/t of 1 cycle (mm) (The standard paper speed is 25 mm/s.)

Example: paper speed = 25 mm/s; t = 1 mm; Fn = (25 mm/s)/1 mm = 25 Hz 2. Determine the amplitude ratio

a. Measure the amplitude (A) in millimeters of 2 successive oscillations (A1, A2). b. Calculate the amplitude ratio: divide A2 by A1 (A2/A1).

3. Determine the dynamic response characteristics On the Fn-versus-amplitude ratio graph a. Plot Fn along the x-axis (result of step 1)

b. Plot the amplitude ratio along the y-axis on the right (result of step 2)

c. Find the intersection of the 2 lines. Where the 2 lines intersect on the Fn-versus-amplitude ratio graph determines if the system is able to correctly reproduce the hemodynamic waveform (adequate, optimal) or if the system is not functioning at a desirable level (overdamped, underdamped, unacceptable).

Figure 1 The 3 steps of dynamic response testing. A, The fast-flush test. B, The frequency-versus-damping coefficient

graph.

A, Adapted from Bridges and Middleton,36with permission. B, Reprinted from Gardner and Hollingsworth,28with permission; adapted from Bridges and Middleton,36 with permission. A B B Period (t) = 1.2 mm A2 = 3 mm A1 = 7 mm Fast flush

(8)

pressure.22,23Under normal condi-tions, 80% of the original wave is thought to be reflected.22

Clinically, wave reflection plays an important role in left ventricu-lar workload and cardiac oxygen consumption. In young adults with elastic arteries, the reflected wave returns to the heart during the diastolic phase of the cardiac cycle and thus augments coronary artery perfusion. In elderly patients or patients with stiff, atheroscle-rotic vessels, the reflected wave returns to the heart during systole and thus increases systolic pres-sure and left ventricular afterload.39

Pharmacological vasoconstriction can similarly increase wave reflec-tion and cardiac workload.23,39

The contribution of reflected waves to the measured systolic pressure is diminished during hypovolemia, hypotension, the Valsalva maneuver, and vasodi-latation.23In pharmacologically induced vasodilation, such as occurs with nitroglycerin for instance, peripherally measured systolic pressure may not change in proportion to the actual degree of reduction in central aortic pres-sure.39,40The effect of nitroglycerin may be visible in the appearance of reflected waves after the systolic peak (Figure 4), but reduced aortic pressure, afterload, and cardiac work load may be more evident through clinical improvement of the patient. During shock with vasoconstriction, wave reflection can lead to the overestimation of central aortic pressure, because peripheral SBP may be 20 mm Hg higher than aortic pressure.36,39 Peripherally measured SBP could in this situation provide a false sense of security that the patient is maintaining adequate perfusion pressures. A slower systolic up-stroke and a prominent diastolic waveform with reflected waves may be visual indicators of shock with vasoconstriction39(Figure 5).

SOURCES OF

ARTIFACT AND

CHANGES IN

WAVEFORM

MORPHOLOGY:

RECOMMENDATIONS

FOR CLINICAL

PRACTICE

Damping, Overdamping, and

Underdamping

A common scenario when working with arterial catheters is comparing the blood pressure recorded by the arterial catheter with the blood pressure obtained manually or with an oscilloscope. If a discrepancy occurs, the arterial catheter is often said to be some-how “damped,” with the underly-ing understandunderly-ing that pressure readings obtained with the cath-eter cannot be trusted. Such an interpretation may be premature and probably disregards several important facts. Differences exist between (1) damping, overdamp-ing, and underdamping; (2) over-damped and underover-damped pres-sure waveforms caused by over-damped or underover-damped moni-toring systems and overdamped-or underdamped-appearing waveforms that reflect the true physiological status of a patient; and (3) blood pressures obtained via direct versus indirect monitor-ing methods.

All hemodynamic monitoring systems are damped. Damping is desired, because without damp-ing the vibrations of the system’s fluid column caused by the arteri-al pressure pulse would go on indefinitely and no accurate waveform could be recorded. Conversely, both overdamped and underdamped systems exist, and their recordings are indeed erroneous. With an overdamped system, the waveform loses its characteristic landmarks and

CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 69 Figure 2 The normal arterial pressure waveform.

MAP indicates mean arterial pressure.

Reprinted from Darovic,10with permission.

Figure 3 Changes of the arterial

pressure waveform configuration throughout the arterial tree. Note the increasing steepness and amplitude of the systolic upstroke and the changing location of the dicrotic notch.

Reprinted from Gorny,8with permission. Central aorta Brachial Radial Femoral Dorsalis pedis

Anacrotic limb Dicrotic limb

Systolic=115 mm Hg Pulse pressure =35 mm Hg Diastolic=80 mm Hg MAP=Area + Base =97 mm Hg Dicrotic notch BASE 120 97 80 40 0

(9)

appears unnaturally smooth, with a diminished or absent dicrotic notch. Overdamping results in falsely low systolic and falsely high diastolic pressure readings26 (Figures 6 and 7). An overdamped-appearing (often simply called damped) waveform can also be the result of aortic stenosis, vasodi-latation, or low cardiac output states such as cardiogenic shock, sepsis, or severe hypovolemia (Figure 5). In order to determine if the waveform is a result of an over-damped system or is an accurate reflection of a patient’s status, the dynamic response characteristics must be tested.

Today’s commercially avail-able catheter-transducer systems

tend to have a low natural fre-quency and consequently are often underdamped.22,36 Anec-dotal reports of manufacturers of an improved natural frequency often do not hold up in clinical practice. Typically, the natural frequency of hemodynamic mon-itoring systems currently on the market is less than 25 Hz. An underdamped system will record falsely high systolic pressures (15-30 mm Hg) and falsely low diastolic pressures26(Figures 8-10). Underdamping, most often in the form of systolic overshoot (the artificial exaggeration of sys-tolic pressure), must be suspect-ed in patients with hypertension, atherosclerosis, vasoconstriction,

aortic regurgitation, or hyperdy-namic states such as fever.23In these conditions, typically a rapid rise in the systolic slope occurs, frequently exceeding the dynam-ic response characteristdynam-ics of the monitoring system. A heart rate greater than 150/min may also cause systolic overshoot, because of the rapid succession of impulses.26

The variable natural frequency of available monitoring systems explains why with different moni-toring systems, different hemody-namic pressures can be measured even though the patient’s condi-tion has not changed.22The often observed discrepancies between directly and indirectly obtained SBP and DBP readings are also partly caused by underdamping.22 Clinically, recognition of pos-sibly overdamped and under-damped waveforms and an awareness of physiological situa-tions when each type of wave-form may occur are important. Then the question to be answered is whether the cause of the waveform is the patient’s condition or the monitoring sys-tem. Practically, the intervention for both overdamped and under-damped systems is the same: maximizing natural frequency.

Techniques for Maximizing

Natural Frequency

As mentioned earlier, air bub-bles are a main factor in wave-form blunting or overdamping. In addition to air bubbles, other fac-tors may alter the natural fre-quency of a monitoring system and distort the recorded signal. These factors include narrow, compliant, and long tubing; pres-ence of additional stopcocks; and loose connections. Translated into practice, the monitoring system

70 CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002

Figure 4 Example of a waveform common in patients with hypertension

(arterial blood pressure, 192/84 mm Hg; pulse pressure, 108 mm Hg). Note the narrow systolic tip, the position of the dicrotic notch (D), and the reflected waves (R). A reflected wave like the first reflected wave after the systolic upstroke may appear with the initiation of nitroglycerin therapy.40

Overall, the arterial waveform appears underdamped, but the dynamic response characteristic is adequate, close to optimal. Natural frequency, 25/1 = 25 Hz; amplitude ratio, 3.5/8 = 0.44.

Figure 5 Waveform in a patient in shock with vasoconstriction. Note slow

systolic upstroke and relatively high diastolic wave with reflection waves (R). The waveform appears overdamped.

(10)

should (1) be primed air-free, (2) consist of wide-bore, high-pres-sure tubing with its length limited to 122 cm (48 in), (3) not be extended with tubing or added stopcocks, and (4) have tightly secured connections.27,36 In addi-tion, the continuous flush bag should be cleared of any air and be maintained adequately filled, and the external pressure cuff sur-rounding the flush solution bag should be maintained at a pres-sure of 300 mm Hg. This practice will not only prevent air from going into the solution but also help prevent catheter clotting.

Catheter clotting is a rare, but possibly serious, complication of intra-arterial monitoring. One of the first indications of clotting may be a waveform that looks over-damped. Whenever waveform overdamping is observed, the

patient should be assessed for signs and symptoms of hypo-tension or low cardiac output. Then, the potential clot should be removed by aspirating blood from the distal stopcock before performing any flushing maneuver for the dynamic response test.37 Fluids with viscosities higher than the viscosity of normal isotonic sodium chloride solution also lead to overdamping of the hemody-namic waveform.23For example, blood in the arterial catheter (due to blood backup or insufficient flushing) should be cleared from the system. As a general rule, the catheter-tubing system and stop-cocks should be flushed before any hemodynamic measurement is performed, especially when clini-cal decisions are to be made. The Table summarizes the most important recommendations for

optimizing the natural frequency of the monitoring system and dynamic response testing.

In general, overdamping and underdamping affect mostly SBP and DBP. MAP is less sensitive to these sources of waveform distor-tion and is therefore less depen-dent on the dynamic response characteristics of the catheter sys-tem.26When all steps have been taken to maximize the natural frequency of a system, yet the dynamic response test indicates overdamping or underdamping, then either MAP should be followed or an alternative method of monitoring (eg, oscillometric blood pressure monitoring) should be used.

End-Hole Artifact

The arterial catheter of the ABP monitoring system points upstream. The forward-flowing blood contains kinetic energy. When the flowing blood is sud-denly stopped by the tip of the catheter, the kinetic energy of the blood is partially converted into pressure. This converted pressure may add 2 to 10 mm Hg to the systolic pressure measured by an intra-arterial monitoring system.23 The artificial augmentation of directly monitored systolic

pres-CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 73 Figure 8 Example of an

underdamped waveform. Natural frequency, 25/1.5 = 16.7 Hz; amplitude ratio, 7/14 = 0.5. Figure 6 Overdamped waveform due to an overdamped monitoring system.

Note the absence of fast-flush oscillations.

Figure 7 Example of an overdamped-appearing waveform. The dynamic response characteristic of the system gives an answer to the question, is the waveform overdamped because of the monitoring system or is it a correct reflection of the patient’s condition?

(11)

CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 75

sure by converted kinetic energy is referred to as the end-hole arti-fact or the end-pressure product.

Movement Artifact

Motion of the tubing system enhances the fluid oscillations of the system. Although the clinical significance of movement artifact is not known, it is recommended that extrinsic movement of the tubing system be kept at an abso-lute minimum.10

Monitor Artifact

The differences (>5 mm Hg) between the digital pressure out-put displayed on the monitor and pressures directly read from analog or strip chart recordings are poten-tially important.43These differences can lead to erroneous data collec-tion and are especially notable in patients with hypotension,

hyper-tension, dysrhythmias, or pulsus paradoxus.43The monitoring sys-tem cannot discriminate between pressure readings during zeroing, obtaining blood samples, and fast-flushing and real arterial pressure readings. Consequently, all readings are incorporated into pressure trends.43Monitoring arti-fact (ie, monitoring noise caused by movement of the patient and disturbances in a monitoring sys-tem due to, for example, electrical heating or cooling blankets) may also be superimposed on the patient’s pressure waveform. Experienced clinicians can recog-nize and eliminate some of these error sources and use a represen-tative set of waveform tracings on a calibrated strip-chart recording to obtain the most valid assess-ment of a patient’s hemodynamic status.43Thus, the optimal method

for hemodynamic pressure mea-surement is to use the analog strip-chart recording.43,44

Respiratory Variation

Normal breathing leads to changes in intrathoracic pressure, which affect cardiac output and systemic pressure. With sponta-neous inspiration, intrathoracic pressure decreases. The de-creased pressure is recognizable on the ABP tracing as a downward displacement of the waveform baseline. Concurrently, during in-spiration, venous return to the right side of the heart is increased, augmenting right ventricular stroke volume. The increase in right ventricular stroke volume is offset by increased pulmonary vas-cular compliance and blood pool-ing durpool-ing inspiratory thoracic expansion. Consequently, left ven-tricular stroke volume is decreased. Heart rate and SVR both increase as a compensatory reflex. The net result of this chain of reflexes is the phenomenon known as physiolog-ical pulsus paradoxus (a decrease in ABP of usually <10 mm Hg dur-ing spontaneous, unassisted inspi-ration).45An inspiratory decrease in ABP greater than 10 mm Hg (pul-sus paradoxus) may indicate car-diac tamponade or restrictive pericarditis. Pulsus paradoxus also occurs in patients with obstructive lung disease, pulmonary em-bolism, and severe heart failure and can be induced by mechanical ventilation.46,47

During positive-pressure venti-lation, the inspiratory increase in intrathoracic pressure can be rec-ognized in the upward displace-ment of the baseline of the arterial pressure waveform. If a patient receiving mechanical ventilation is hypovolemic, the increase in

Figure 9 Example of an underdamped waveform. Natural frequency, 25/2 = 12.5 Hz; amplitude ratio, 4/11 = 0.36. Note the normal-appearing fast-flush oscillations.

Figure 10 Example of an overdamped-appearing waveform. However, the

dynamic response test places the system on the border between

underdamped and adequate. Natural frequency, 25/1.8 = 13.9 Hz; amplitude ratio, 9/19 = 0.47.

(12)

76 CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 intrathoracic pressure may lead to

artificial augmentation of directly monitored SBP.

Current monitoring systems determine the mean of pressure readings at predetermined inter-vals. Respiratory artifact could lead to erroneous digital output data. The unpredictable effect of respira-tory variation on arterial pressure provides a strong argument for reading and recording arterial pres-sure, like any other hemodynamic index, at the end of expiration by using a freeze-frame picture or, best, a strip-chart recording.48,49

Hypertension and

Atherosclerosis

Hypertension is due to age-related arterial stiffening, athero-sclerotic narrowing, or renin-related vasoconstriction, all of which increase the magnitude of reflected waves. In these physiolog-ical conditions, reflected waves fuse with the systolic upstroke,

resulting in a high pulse pressure and late high systolic peak,39often manifested as a narrow systolic peak in the peripheral ABP wave-form tracing.10,38In addition, the diastolic wave may be reduced or disappear.39Figures 4 and 11 show peripheral ABP tracings typical in patients with hypertension or atherosclerosis. In each instance, the small and narrow tip of the

waveform may be an overesti-mation of systolic pressure and thereby central aortic pressure. As explained earlier, hypertension and atherosclerosis place high demands on the monitoring sys-tem. The arterial waveforms shown in Figures 4 and 11 could also be the result of systolic over-shoot due to inadequate dynamic response characteristics of the

Figure 11 Example of a waveform common in patients with hypertension

(arterial blood pressure, 150/45 mm Hg). Note steep systolic upstroke, narrow systolic peak, diminished diastolic run-off wave, and relative decrease in the diastolic proportion of the waveform due to a heart rate of 100/min. The waveform appears underdamped.

Recommendations for optimizing the natural frequency of the arterial pressure monitoring system and dynamic response testing

Natural frequency of the monitoring system23,27,41

Dynamic response test27,41

Feature

System requirements

Use wide-bore, high-pressure tubing no longer than 122 cm (48 in) Avoid tubing extensions and minimize stopcocks

Ensure that all connections are tightened

Eliminate air from the flush fluid and air bubbles from the tubing system Keep continuous flush bag filled and keep external pressure cuff at 300 mm Hg

pressure

Clear access catheter and tubing system of any fluid other than isotonic sodium chloride solution

Prevention of catheter clotting

Maintain continuous flush device as described Use heparinized flush solution42

Prevention of catheter kinking

Keep cannulated extremity in a neutral or slightly extended position Implementation of test

Whenever the waveform seems overdamped or underdamped Whenever physiological changes of the patient (increased heart rate,

vasoconstriction) place higher demands on the monitoring system After opening the system

Before implementing interventions or changes of interventions

Whenever the accuracy of the arterial blood pressure measurement is in doubt At least every 8-12 hours

(13)

monitoring system. The result of the dynamic response test provides reassurance that the recorded ABP tracing is correct.

MAP is measured as the area under the pressure curve divided by the width of the base of the pressure curve (the time interval of a single cardiac cycle)10,37 (Figure 2). A small and narrow systolic tip such as the ones in Figures 4 and 11 adds relatively little to the total area under the pressure curve, whereas it can add significantly to measured SBP. Consequently, the measured MAP is less affected by wave reflection and the response char-acteristics of the monitoring sys-tem than is measured SBP. The MAP remains relatively constant when measured at different sites throughout the arterial circuit, whereas measured SBP and DBP may differ.10In general, MAP is a more stable hemodynamic para-meter and provides a more accu-rate interpretation of a patient’s hemodynamic status.10,34,36,38

INDIRECT VERSUS

DIRECT ABP

MONITORING

A discussion of the various methods of indirect ABP mea-surement and how they compare with direct ABP monitoring is beyond the scope of this article. However, several key principles should be emphasized in this context. Direct ABP monitoring measures pressure pulse, whereas all indirect methods of ABP mea-surement are related to blood flow. No absolute relationship exists between these 2 phenome-na because they follow different laws of physics and physiology. In low-flow conditions, such as hypotension and vasoconstricted states, indirect methods yield

lower pressure readings than does direct ABP monitoring.22,36 Con-versely, if SVR is low, in patients with sepsis for instance, the rela-tively high flow results in an indi-rect ABP reading that is higher than the directly measured ABP.22,36Factors such as under-damping, end-hole artifact, and wave reflection contribute to direct systolic pressure readings that are often higher than indi-rectly obtained pressure values. In other words, when obtaining ABP readings by using different measuring methods, different results should be expected. More specifically, a “good” correlation between the oscilloscope and the arterial pressure monitoring sys-tem is not a gauge for the proper functioning of the pressure moni-toring system. MAP, on the con-trary, is closely approximated when oscillometric and direct measurements are compared.21-25,36 Although both the oscillomet-ric and the direct ABP monitoring methods are generally accurate in clinical practice, direct ABP moni-toring has a distinct advantage. Direct ABP monitoring is the only scientifically and clinically vali-dated method that allows real-time and continuous monitoring of a patient’s ABP. With strip-chart recording, beat-to-beat analysis of a patient’s ABP is pos-sible. This feature may be of clini-cal relevance when evaluating the effect of positive end-expiratory pressure during mechanical ven-tilation or the effect of changing stroke volume in atrial fibrillation or other arrhythmias.

SUMMARY

Hemodynamic monitoring is a costly procedure, both materially and with regard to nursing time

involved to ensure proper func-tioning of the monitoring system and correct interpretation of the data obtained. Dynamic response testing is the ideal method of con-firming the ability of a monitoring system to accurately reproduce hemodynamic waveforms. MAP is a stable hemodynamic parameter, because it is least affected by moni-toring method, catheter insertion site, the dynamic response charac-teristics of the catheter system, and wave reflection. MAP provides the best estimate of central aortic pres-sure and is the main hemodynamic parameter monitored by the neu-rohormonal system to control blood pressure. The superior infor-mational value of MAP provides strong support for its preferred use in clinical practice, especially when use of vasoactive drugs is started or the dosages of these drugs are titrated.10,21However, numerically satisfactory ABP or MAP values are not necessarily related to adequate peripheral tissue perfusion and organ system function. For optimal management of patients, data obtained from assessment tools such as hemodynamic monitoring devices must be integrated with information gained from clinical assessment of patients’ status. ✙

Acknowledgments

I (B.H.M.) am grateful to Maj Bridges for sharing her expertise and for her help and support in preparing this article.

References

1. McGhee BH, Woods SL. Critical care nurs-es’ knowledge of arterial pressure moni-toring. Am J Crit Care. 2001;10:43-51. 2. Bridges EJ. Evaluation of Critical Care

Nurses’ Knowledge and Ability to Utilize Information Related to Pulmonary Artery Pressure Measurement [master’s thesis]. Seattle, Wash: University of Washington; 1991.

3. Kondrat P. Critical Care Nurses’ Knowledge of Pressure Waveforms Obtained From the Pulmonary Artery Catheter [master’s thesis]. Seattle, Wash: University of Washington; 1994. 4. Iberti TJ, Daily EK, Leibowitz AB,

Schecter CB, Fischer EP, Silverstein JH. Assessment of critical care nurses’

(14)

CRITICAL CARENURSE Vol 22, No. 2, APRIL 2002 79 edge of the pulmonary artery catheter.

The Pulmonary Artery Catheter Study Group. Crit Care Med. 1994;22:1674-1678. 5. Burns D, Burns D, Shively M. Critical care nurses’ knowledge of pulmonary artery catheters. Am J Crit Care. 1996; 5:49-54.

6. Rhoades RA, Tanner GA. Medical Physiology. Boston, Mass: Little Brown & Co; 1995.

7. Scher A, Feigl EO. Introduction and physical principles. In: Patton D, Fuchs AF, Hille B, Scher AM, Steiner R, eds. Textbook of Physiology. Vol 2. 21st ed. Philadelphia, Pa: WB Saunders Co; 1989:771-781.

8. Gorny DA. Arterial blood pressure mea-surement technique. AACN Clin Issues. 1993;4:66-80.

9. Halpenny C. The systemic circulation. In: Woods SL, Sivarajan-Froelicher ES, Halpenny C, Motzer S, eds. Cardiac Nursing. 3rd ed. Philadelphia, Pa: JB Lippincott; 1995:58-71.

10. Darovic GO. Hemodynamic Monitoring: Invasive and Noninvasive Clinical Application. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1995.

11. Bridges EJ. The systemic circulation. In: Woods SL, Motzer S, Sivarajan-Froelicher ES, eds. Cardiac Nursing. 4th ed. Philadelphia, Pa: JB Lippincott; 1999:51-71.

12. Nutter D. Measurement of the systolic blood pressure. In: Hurst J, ed. The Heart, Arteries, and Veins. 5th ed. New York, NY: McGraw-Hill; 1982:182-187. 13. O’Rourke MF. The measurement of

sys-temic blood pressure: normal and abnormal pulsations of the arteries and veins. In: Hurst J, Schlant R, eds. The Heart, Arteries, and Veins. 7th ed. New York, NY: McGraw-Hill; 1990:149-162. 14. Bridges EJ. Control of blood pressure

and cardiac output. In: Woods SL, Motzer S, Sivarajan-Froelicher ES, eds. Cardiac Nursing. 4th ed. Philadelphia, Pa: JB Lippincott; 1999:82-106. 15. Hedges JR. Preload and afterload

revisit-ed. Emerg Nurs. 1983;9:262-267. 16. O’Rourke MF. What is blood pressure?

Am J Hypertens. 1990;3:803-810. 17. Folkow B, Svanborg A. Physiology of

car-diovascular aging. Physiol Rev. 1993;73:725-764.

18. Franklin S, Gustin W, Wong N, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation. 1997;96:308-315.

19. Lakatta E. Cardiovascular system. In: Masora E, ed. Handbook of Physiology: Aging. Bethesda, Md: American Physiological Society; 1995:413-474. 20. Feigl EO. Coronary circulation. In:

Patton HD, Fuchs AF, Hille B, Scher AM, Steiner R, eds. Textbook of Physiology. Vol 2. 21st ed. Philadelphia, Pa: WB Saunders Co; 1989:933-950.

21. Marino PL. The ICU Book. Philadelphia, Pa: Lea & Febiger; 1998.

22. Henneman E, Henneman P. Intricacies of blood pressure measurement. Heart Lung. 1989;19:263-273.

23. Grossman W. Pressure measurement. In: Grossman W, Baim D, eds. Cardiac Catheterization, Angiography and Intervention. 5th ed. Baltimore, Md: Williams & Wilkins; 1996:125-142. 24. Venus B, Mathru M, Smith RA, Pham

CG. Direct versus indirect blood pres-sure meapres-surements in critically ill patients. Heart Lung. 1985;14:228-231.

25. Loubser PG. Comparison of intra-arteri-al and automated oscillometric blood pressure measurement methods in post-operative hypertensive patients. Med Instrum. 1986;20:255-259.

26. Gardner RM. Direct blood pressure mea-surement: dynamic response require-ments. Anesthesiology. 1981;54:227-236. 27. Gibbs N, Gardner RM. Dynamics of

invasive pressure monitoring systems: clinical and laboratory evaluation. Heart Lung. 1988;17:43-51.

28. Gardner RM, Hollingsworth K. Optimizing the electrocardiogram and pressure monitoring. Crit Care Med. 1986;14:651-658.

29. Kee L, Simonson J, Stotts N, Skov P, Schiller N. Echocardiographic determi-nation of valid zero reference levels in supine and lateral positions. Am J Crit Care. 1993;2:72-78.

30. Winsor T, Burch GE. Phlebostatic axis and phlebostatic level: reference levels for venous pressure measurement in man. Proc Soc Exp Biol Med. 1945;58:165-169.

31. Bartz B, Maroun C, Underhill S. Dif-ferences in mid-anterioposterior level and midaxillary level in patients with a range of chest configurations. Heart Lung. 1988;17:308.

32. Bridges EJ, Bond EF, Ahrens T, Daly E, Woods SL. Direct arterial vs oscillometric monitoring of blood pressure: stop com-paring and pick one. Crit Care Nurse. December 1997;17:96-97, 101-102. 33. Ahrens T, Penick J, Tucker M. Frequency

requirements for zeroing transducers in hemodynamic monitoring. Am J Crit Care. 1995;4:466-471.

34. Gardner RM, Hujcs M. Fundamentals of physiologic monitoring. AACN Clin Issues. 1993;4:11-24.

35. Hoover L. Comparison of blood pressure readings between cuff pressures and radial arterial catheters with changes in transducer level and patient position [abstract]. Am J Crit Care. 2000;9:220-221. 36. Bridges EJ, Middleton R. Direct arterial vs oscillometric monitoring of blood pressure: stop comparing and pick one (a decision-making algorithm). Crit Care Nurse. June 1997;17:58-66, 68-72. 37. Campbell B. Arterial waveforms:

moni-toring changes in configuration. Heart Lung. 1997;26:204-214.

38. Gardner PE, Bridges EJ. Hemodynamic monitoring. In: Woods SL, Sivarajan-Froelicher ES, Halpenny C, Motzer S, eds. Cardiac Nursing. 3rd ed. Philadelphia, Pa: JB Lippincott; 1995:424-458.

39. O’Rourke MF, Yaginuma M. Wave reflec-tions and the arterial pulse. Arch Intern Med. 1984;144:366-371.

40. O’Rourke MF. Arterial mechanics and wave reflection with antihypertensive therapy. J Hypertens. 1992;10:43-49. 41. Imperial-Perez F, McRae M. Arterial

Pressure Monitoring. Aliso Viejo, Calif: American Association of Critical-Care Nurses; 1998.

42. Evaluation of the effects of heparinized and nonheparinized flush solutions on the patency of arterial pressure monitor-ing lines: the AACN Thunder Project. Am J Crit Care. 1993;2:3-15.

43. Maloy L, Gardner RM. Monitoring sys-temic arterial blood pressure: strip chart recording versus digital display. Heart Lung. 1986;15:627-635.

44. Lundstedt JL. Comparison of methods of measuring pulmonary artery pressure.

Am J Crit Care. 1997;6:324-332. 45. Ellis D. Interpretation of beat-to-beat

blood pressure values in the presence of ventilatory changes. J Clin Monit. 1985;1:65-70.

46. Christensen B. Hemodynamic monitor-ing: what it tells you and what it doesn’t, I. J Post Anesth Nurs. 1992;7:330-337. 47. Topol E, ed. Textbook of Cardiovascular

Medicine. Philadelphia, Pa: Lippincott-Raven Publishers; 1998.

48. Daily E, Speer-Schroeder J. Techniques in Bedside Hemodynamic Monitoring. St Louis, Mo: Mosby-Year Book Inc; 1994. 49. Nora A, Burns M, Downs W. Blood

Pressure. Richmond, Wash: Space Labs Medical Inc; 1993.

References

Related documents

It not only reduces carbon footprint, but the improvement in the strength of the concrete also allows the reduction of cement used in order to achieve

treatment combinations were attributed due to the ratios variation of cow milk &amp; buffalo milk, baking temperature and baking periods of ChhanaPodo.. Difference in the

The 19 years dataset of Orang station is divided into two parts: (i) the first 18 years (1984- 2003) of data are used in the phase-space identification and (ii) the subsequent 1 year

using these personal devices to perform their duties, what is now referred to as the “bring your own device” (BYOD) revolution. Contain yourself: top five ways to protect

SUC 1 was internationalized to a very great extent (5) on indicators in Curriculum and Instruction, and in Diverse Income Generation and to a great extent (4)

We postulate this patient developed multiple irAEs, including progressive atopic dermatitis, vitiligo, tubulointerstitial nephritis, autoimmune hepatitis, and an NMDA-R Ig

This has been the case with leukemic children, and it appears to be the case from our experience even with healthy children.. uated and attenuation was not a result of injecting it by