Hematocrit level correlates with lungs resistivity in elderly patients with cardiogenic pulmonary edema

doi:10.4236/jbise.2011.41010

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J. Biomedical Science and Engineering, 2011, 4, 76-81

doi:10.4236/jbise.2011.41010 Published Online January 2011 (http://www.SciRP.org/journal/jbise/

JBiSE

Published Online January 2011 in SciRes. http://www.scirp.org/journal/JBiSE

Hematocrit level correlates with lungs resistivity in elderly

patients with cardiogenic pulmonary edema

Marina Arad1, Avraham Adunsky1, Sharon Zlochiver2, Ofer Barnea2, Shimon Abboud2

1Department of Geriatric Rehabilitation Sheba Medical Center, Tel-Hashomer, and Sackler Faculty of Medicine, Tel Aviv University,

Tel Aviv, Israel; 2Department of Biomedical Engineering; Tel-Aviv University, Tel Aviv, Israel.

Email: [email protected]

Received 17 September 2010; revise 22 September 2010; accepted 26 September 2010.

ABSTRACT

Regular monitoring of pulmonary congestion in car-

diogenic pulmonary edema (CPE) patients is neces-

sary for its adequate management via pharmaceuti-

cal treatment. It is well known that the development

of CPE is accompanied with an increase in hema-

tocrit, plasma protein concentration and colloid os-

motic pressure due to the decrease in the plasma

volume. In the present study the mean left and right

lung resistivity values taken pre- and post treatment

with diuretics using a hybrid bio-impedance electri-

cal impedance tomography system were correlate to

the measured changes in hematocrit level. A marginal

significant correlation was found between the abso-

lute mean lung resistivity and hematocrit levels

(Pearson’s correlation coefficient of R = 0.4, p-value =

0.057). When the change in the mean lung resistivity

of a patient was plotted vs. the change in hematocrit

readout, a significant linear corr elation was found (R =

0.7, p-value = 0.02). These results support the validity

of the resistivity measurements using bio-impedance

system in monitoring changes of pulmonary edema in

CPE patients.

Keywords: Bio-impedance; Parametric EIT; Cardiogenic

Pulmonary Edema; Hematocrit

1. INTRODUCTION

Congestive heart failure and a consequent CPE are a

major health problem in the western world. Cardiogenic

pulmonary edema (CPE) is a pathological condition in

which extravasation of fluid and colloid from the pul-

monary capillaries into the interstitium and alveoli of the

lungs occurs as a result of increased hydrostatic pressure

in these capillaries that exceeds the plasma oncotic

pressure. This happens when the heart’s function is im-

paired (heart failure) in conditions such as pulmonary

venous outflow obstruction, left ventricular failure,

ischemic heart disease, myocardial infarction or left

atrial myxoma tumor, to the effect that blood cannot be

sufficiently pumped in proportion to the tissues’ meta-

bolic demand. As a result, a compensatory increase in

pulmonary venous pressure is developed [1,2].

The development of CPE is accompanied with an in-

crease in hematocrit, plasma protein concentration and

colloid osmotic pressure due to the decrease in the

plasma volume. In a study conducted on 95 CPE patients

and 71 control subjects, a significant difference in he-

matocrit level was found between the two groups (44.3

vs. 42.1% for the CPE and control groups, respectively).

Moreover, a gradual decrease in the hematocrit level was

observed for the CPE group during therapy for those

patients whose condition was improved post-treatment

(from 44.5  0.8 to 41.3  0.8%, n = 65) [3]. Similar

results were observed by the same research group in an

additional study [4]. In that study, the effect of CPE

therapy using furosemide, morphine and oxygen on

various plasma parameters was measured in CPE pa-

tients. A statistically significant decrease in hematocrit

from 42.8  1.9 to 36.7  1.8% was found after an aver-

age of 21.3 hours of treatment (n = 10, p-value < 0.001).

This decrease was in conjunction with a difference be-

tween the urine output and fluid intake of 2.823  0.848l.

Further demonstration for the correlation between the

lungs fluid volume and hematocrit was given in another

study conducted on a group of 10 CPE patients that were

treated with large doses on intravenous furosemide [5].

In that study, hemodilution was detected 2 hours after

the start of treatment, resulting in a significant reduction

of blood viscosity and hematocrit. The hematocrit was

reduced by a mean of 3% and 5.4% at 30 and 120 min-

utes after the start of treatment.

The gradual filling of the lungs with fluids during the

development of CPE results in substantial changes in the

electric impedance of the lungs, as the lung fluids exhibit

higher conductivity in relation to the electrically insulat-

ing air. Since the lungs are the largest in volume organ in

M. Arad et al. / J. Biomedical Science and Engineering 4 (2011) 76-81

the thoracic volume, such impedance changes are ex-

pected to be large enough to be non-invasively detected

on the body surface via impedance measurement.

Therefore, the bio-impedance technique may be utilized

as an alternative non-invasive CPE monitoring method.

We previously reported on a newly developed hybrid

EIT system (CardioInspect, Tel-Aviv University, Israel)

that combines principles from the bio-impedance and

EIT techniques and enables the reconstruction of the

separate left and right lung resistivity values. The sys-

tem’s performance was studied on both healthy and CHF

patients, and its capability to diagnose and monitor pa-

tients was demonstrated [6-10]. Here we examine the

correlation between the measured left and right lung

resistivity values to the hematocrit level in a group of

CHF patients during diuretics treatment.

2. METHODS

2.1. Clinical Study

A clinical study was conducted in the geriatric depart-

ment in Tel-Hashomer hospital, Ramat-Gan, Israel. The

study included 12 CHF patients (n = 4/8, male/female,

mean age 78  10 years) that were diagnosed and found

having pulmonary edema and were under monitoring

and CPE management. All participants signed an in-

formed consent form, and the study was approved by the

local Helsinki committee. Two bio-impedance meas-

urements were taken. The first measurement was taken

as a reference measurement to determine the lungs’ re-

sistivity value pre-treatment. The second measurement

was taken following treatment with diuretics, morphine

and oxygen. In addition to the bio-impedance measure-

ments, blood samples were taken at the two measuring

times, and hematocrit level was assessed as part of a

complete blood count. All bio-impedance measurements

were taken shortly after the patients were asked to sit

rested to ensure shallow tidal respiration and minimal

body movements that may impair reproducibility of the

results.

2.2. Bio-impedance System

We employed the portable PulmoTrace hybrid bio-im-

pedance measurement system (CardioInspect, Tel-Aviv

University, Tel-Aviv Israel). The system has been previ-

ously studied and described in detail [6-10]. Briefly, the

system comprises of three units (Figure 1): 1) an

8-electrode belt is attached around the patient’s chest at

the plane of the fifth intercostals space in the mid-

clavicular line. The electrodes are Ag/AgCl disposable,

and they are attached at equal angular distance from

each other using 8 adjustable elongation segments on

the belt; 2) an analog unit generates the injection current

(3 mA ptp, 20 kHz) and directs the current through a

Figure 1. PulmoTrace hybrid bio-impedance measurement

system.

demultiplexer to the appropriate pair of electrodes. The

developing voltages at the rest of the electrodes are

measured differentially, amplified, filtered and digitized

for analysis. The current injection is done in the opposite

injection scheme, i.e. a total of 4 injections is performed,

for each 5 voltages are measured with the remaining 6

electrodes, yielding 20 independent measurements; and

3) an interface unit includes a microprocessor that proc-

esses the digitized voltage measurements and solves a

parametric inverse-problem to estimate the left and right

lung resistivity values. The reconstruction algorithm is

based on an iterative, parameterized Newton-Raphson

inverse solver as previously reported [6]. The results are

shown on an LCD screen, and can be printed out. The

system is powered by a rechargeable battery to ensure

electrical safety in the hospital environment. A custom

ECG signal is taken by the system prior to the bio-im-

pedance measurements, in order to synchronize the cur-

rent injections and surface voltage measurements to the

iso-potential phase of the ECG, so that to ensure a simi-

lar heart geometrical configuration between measure-

ments. The entire measurement procedure lasts less than

1 minute and completely painless.

2.3. Statistics

Data were fitted using linear regression, and Pearson’s

correlation coefficient was computed to check the strength

of linear dependence. The significance of correlation was

assessed using a transformation into t-statistics. A p-value

of less than 0.05 was considered statistically significant.

3. RESULTS

Table 1 summarizes the bio-impedance and hematocrit

measurements that were taken for all 12 patients at the

two measuring phases–pre-treatment (reference) and

M. Arad et al. / J. Biomedical Science and Engineering 4 (2011) 76-81

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Table 1. Bio-medical and hematocrit level measurements.

Patient # Sex Age Reference measurement Post-treatment measurement

Mean lung resistivity

[Ω cm]

HCT Level

(%) Mean lung resistivity

[Ω cm] HCT Lev el

(%)

1 F 92 853 38.6 800 39.6

2 M 80 1083 44.9 1231 43.1

3 F 91 824 31 889 33.2

4 F 73 715 33.3 834 36.9

5 M 69 625 38.2 675 36.1

6 F 69 861 29.2 1200 38

7 F 88 1060 35.8 1061 33.2

8 F 77 771 34.5 852 33.6

9 F 83 660 28.3 753 30.5

10 M 84 884 41.5 935 41.5

11 F 81 996 35.1 1089 38.1

12 M 58 871 43.4 859 44.3

post-treatment. A two-sample paired t-test showed that

the mean lung resistivity was significantly different be-

tween the two measurements: 850.3  145.6 vs. 931.5 

176.1 Ω cm, pre- and post-treatment, respectively

(p-value = 0.016); on the other hand, the hematocrit lev-

els between the measurements were not significantly

different: 36.2  5.4% vs. 37.3  4.3%, pre- and

post-treatment, respectively (p-value = 0.217). A linear

regression analysis showed marginal significant correla-

tion between the absolute mean lung resistivity and he-

matocrit levels, when all 24 measurements were pooled

together, with a Pearson’s correlation coefficient of R =

0.4 (p-value = 0.057), see Figure 2. However, when the

change in the mean lung resistivity of a patient was

plotted vs. the change in hematocrit readout, a signifi-

cant linear correlation was found as can be seen in Fig-

ure 3 (R = 0.7, p-value = 0.02).

4. DISCUSSION

In this work, we have correlated the bio-impedance

measurements of a group of CPE elderly patients with

the hematocrit level, pre- and post treatment with diuret-

ics in order to study the feasibility of the system in

monitoring CPE management in these patients. The

bio-impedance measurements were performed with a

novel hybrid bio-impedance measurement system (Pul-

moTrace by CardioInspect). Proper management of CPE

includes routine monitoring the patient’s condition and

administration of preload and/or afterload reduction

drugs, most notably loop diuretic agents (such as fu-

rosemide) in order to remove excessive lung fluids via

urine passing. Over dosage of diuretics, however, may

generate negative effects such as hypovolemia that re-

duces cardiac output, as well as hypokalemia due to re-

duced concentration of potassium in the blood circula-

tion. As a consequence, high efficacy of diuretics treat-

ment for managing CPE is tightly linked to a sensitive

and continuous monitoring of the level of lung fluids

[11].

At present, pulmonary edema severity level is moni-

tored either invasively or non-invasively. Invasive meth-

ods, e.g. single or double thermal die dilution and direct

measurement of the capillary wedge pressure, require

catheterization, and are therefore intrusive, may result in

medical complications and can only be employed in

clinical conditions during hospitalization. The thermal

die dilution technique is also subject to errors in condi-

tions such as pulmonary vascular perfusion or unilateral

lung disease, and despite being considered gold-standard

has low accuracy of 20-30% [12]. Non-invasive methods

are comprised of imaging systems, most notably X-ray

radiographs, computerized tomography (CT) and mag-

netic resonance imaging (MRI). While X-ray radio-

graphs are widely practiced, their sensitivity and accu-

racy are inconsistent and subjective [13,14], especially

in cases of coexisting pulmonary diseases [15]. On the

other hand, high resolution imaging achieved by CT or

MRI provides high accuracy in measuring lung fluids of

M. Arad et al. / J. Biomedical Science and Engineering 4 (2011) 76-81

Figure 2. Correlation between mean lung resistivity value and

hematocrit (n = 24, R = 0.4, p-value = 0.057).

Figure 3. Correlation between mean lung resistivity value

change and hematocrit change (n = 12, R = 0.7, p-value = 0.02).

~3%, but cannot be utilized routinely due to either high

ionizing radiation or the large expenses involved.

The bio-impedance technique has been proposed al-

ready in the late 1960’s for evaluating the lungs fluid

volume. Global measurements of the transthoracic im-

pedance as an indirect marker for lungs fluid level was

performed by Pomeranz et al. (1969, 1970) on a canine

model [16,17]. In a common transthoracic measurement

configuration, low magnitude and frequency electrical

current is injected via a pair of electrodes and the devel-

oping voltage between the thorax extremities is simulta-

neously measured, either by the same pair of electrodes

or by a different pair of electrodes (2 or 4 electrode con-

figuration, respectively). During the last decades, nu-

merous experimental and clinical studies have employed

and improved the global transthoracic impedance meas-

urement for monitoring pulmonary edema, in both ani-

mal and human models [18-21]. The technique was also

commercialized, e.g. the BioZ system (CardioDynamics,

San Diego, CA) that extracts thoracic fluid content and

additional hemodynamic and cardiac parameters [22].

Despite the attractiveness of the transthoracic bio-im-

pedance technique for monitoring lungs fluid volume, a

major disadvantage is that the technique provides only a

global mark of average thoracic impedance, and the rela-

tive contributions of the various thoracic organs or even

the separate lung lobes to the measured value cannot be

assessed. A tomographic variation of the bio-impedance

technique for pulmonary function evaluation was first

presented in the mid 1980’s, with the development of the

electrical impedance tomography (EIT) systems [23-25].

These systems can provide a tomographic image of the

electrical impedance spatial distribution in a 2D slice of

the thorax, or even in a 3D volume. EIT is based on se-

quential injection of current via different pairs of elec-

trodes that are located along the thoracic perimeter, and

measurement of the surface voltages with the rest of the

electrodes. The data provided for the various directions

of injections enable utilization of reconstruction algo-

rithms (linear or non-linear) that solve the so-called “in-

verse-problem” of EIT, i.e. the estimation of the internal

distribution of impedance that is most probable to result

in the set of measured voltages. Various custom-built

EIT systems were studied in both animal and human

models [26-28]; however, this method seems to suffer

from low resolution reconstructions, uneven spatial sen-

sitivity to conductivity perturbations, artifacts arising

from numerical reconstruction errors and extremely low

signal to noise errors [29]. Most of these limitations are

inherent to EIT, due to the mathematical ill-posedeness

of the inverse-problem that is solved. The hybrid system

that was employed here overcomes the major limitation

of EIT systems by employing the inverse problem algo-

rithm to reconstruct only two parameters–the left and the

right lung resistivity values. As a result, the reconstruc-

tion problem becomes well-posed, and the optimization

algorithm is robust, with minimized sensitivity to meas-

urement noises, either geometrical or electrical [6].

In our previous studies we have shown that the system

reproducibility on healthy subjects is <2%, for both

within and between tests, with measured signal-to-noise

ratio of ~75dB [6]. We also demonstrated that the system

doesn’t show dependency on various anthropometric

parameters (e.g. body-mass index, age, height and

weight). In other studies we found good diagnostic

separation capability between healthy subjects and CHF

patients, and long-term monitoring of CPE management

was validated by tracing the measurements during pa-

tient treatment and comparing the bio-impedance meas-

urements to various indirect measures for pulmonary

M. Arad et al. / J. Biomedical Science and Engineering 4 (2011) 76-81

congestion e.g. urine output [8] and X-ray diagnosis [9].

In contrast to the hematocrit, the mean lung resistivity

value was found to be significantly different between the

two measurement phases in the CPE patients (i.e., meas-

urements taken pre- and post-treatment, p-value = 0.016).

Nevertheless, the results in this study show a significant

correlation between the changes in the measured mean

lung resistivity value by the hybrid EIT system to

changes in hematocrit level following diuretic treatment

of CPE patients (R = 0.7, p-value = 0.02). As a conse-

quence, the validity of lung resistivity measurements by

the system is further supported, and it is proposed that

bio-impedance measurements such as those taken in this

study may be a non-invasive, cost-efficient and pa-

tient-friendly supplement or alternative to other moni-

toring methods for pulmonary congestion.

This study is preliminary and consists of a small num-

ber of subjects, resulting in a large variability in the

changes of mean lung resistivity. Nevertheless, encour-

aging results in this study show a significant correlation

between the changes in the measured mean lung resistiv-

ity value by the hybrid EIT system to changes in hema-

tocrit level following diuretic treatment of CPE patients.

A follow-up large scale study that would address these

limitations would be a subject of a further research.

5. ACKNOWLEDGEMENTS

This work was partially supported by a grant from the ELA KODESZ

Institute for Cardiac Physical Sciences and Engineering.

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