Peripheral tissue oxygenation improves during ED treatment of acute heart failure

Unlabelled imageTissue oxygenation improves d”>American Journal of Emergency Medicine (2012) 30, 196-202

Brief Report

Peripheral tissue oxygenation improves during ED treatment of acute heart failure?,??

Christopher J. Hogan MD a,b,c,?, Kevin R. Ward MD a,b, Michael C. Kontos MD b,d,

Leroy R. Thacker PhD e, Roland Pittman PhD b,f

aDepartment of Emergency Medicine, Virginia Commonwealth University Medical Center, Medical College of Virginia Campus, Richmond, VA 23238-0401, USA

bVirginia Commonwealth University Reanimation Engineering Science Center (VCURES), Virginia Commonwealth University

Medical Center, Richmond, VA 23238-0401, USA

cDepartment of Surgery, Division of Critical Care/Trauma, Virginia Commonwealth University Medical Center,

Medical College of Virginia Campus, Richmond, VA 23238-0401, USA

dVirginia Commonwealth University Pauley Heart Center, Medical College of Virginia, Campus, Richmond,

VA 23238-0401, USA

eDepartment of Biostatistics, Virginia Commonwealth University, Richmond, VA 23238-0401, USA

fDepartment of Physiology, Virginia Commonwealth University, Richmond, VA 23238-0401, USA

Received 27 August 2010; revised 18 October 2010; accepted 19 October 2010


Objective: The objective of the study was to quantitatively characterize peripheral tissue microvascular oxygenation during emergency department (ED) treatment of acute heart failure .

Methods: This prospective, observational study enrolled acutely decompensated HF patients presenting to an urban ED and stable, asymptomatic HF patients evaluated in an outpatient cardiology clinic. Stable, pre-ED treatment, and post-ED treatment microvascular oxygen extraction ratios (OERMs) were calculated, defined as SaO2 – StO2/0.8*SaO2, where SaO2 is pulse oximetry-derived arterial hemoglobin saturation and StO2 is the tissue hemoglobin oxygen saturation measured with differential absorption spectroscopy. The OERM measurements were analyzed using repeated-measures analysis of variance. Pulse oximetry, patient demographics, HF etiology, serum B-type natriuretic peptide, and hemoglobin were measured along with a Visual analogue scale to assess patient baseline characteristics and response to ED treatment (P b .05 was considered significant for all testing).

Results: The OERM for the stable HF group (n = 45) was 0.65 (SE = 0.07). The pre- and posttreatment OERMs for the ED HF group (n = 46) were 0.92 (SE = 0.07) and 0.75 (SE = 0.06), respectively. Whereas the pretreatment ED OERM was higher than the stable patient OERM (P = .001), the posttreatment ED OERM was not significantly different from the stable patient measurement (P = .271).

? This study was supported by a General Clinical Research Center Clinical Research Feasibility fund (National Center for Research Resources, National Institutes of Health M01 RR00065).

?? Preliminary parts of this study were presented in abstract form at the Society of Academic Emergency Medicine Annual Meeting on May 17, 2007, in

Chicago, IL.

* Corresponding author. Department of Emergency Medicine, Department of Surgery, Division of Critical Care/Trauma, Virginia Commonwealth University Medical Center, PO Box 980401, Richmond, VA 23238-0401, USA. Tel.: +1 804 828 5250; fax: +1 804 828 4994.

E-mail address: [email protected] (C.J. Hogan).

0735-6757/$ – see front matter (C) 2012 doi:10.1016/j.ajem.2010.10.019

Conclusions: Oxygen extraction in Acute HF is significantly increased, but approaches values found in the stable HF population after ED treatment. The OERM may deserve closer examination as a possible goal-directed variable in the treatment of acute HF.

(C) 2012


heart failure diagnosis and treatment are frequent emergency department (ED) presentations. Emergency department evaluation and treatment have traditionally used global assessors of cardiac function such as serum B- type natriuretic peptide (BNP) measurement, chest radio- graphs, and urine output. However, they poorly reflect treatment response [1-4].

From a physiological standpoint, regional tissue oxygen- ation abnormalities should precede global abnormalities and therefore allow earlier identification of HF severity and response to treatment. Prior work demonstrated that microvascular perfusion is severely altered in HF patients [5]. The microvascular oxygen extraction ratio (OERM) uses noninvasive technology that quantitatively measures micro- vascular tissue oxygen utilization. Our study objective was to assess microvascular oxygenation in HF patients by measuring peripheral tissue OERM in acutely decompensated HF patients before and after treatment, which were compared with that in stable outpatient HF patients.


This prospective, observational study was approved by our institutional review board and randomly enrolled nonconsecutive patients from November 2004 to January 2008 at an urban tertiary care hospital. Decompensated HF patients were enrolled after ED presentation. Inclusion criteria included a prior HF diagnosis, serum BNP greater than 100 ng/mL (ADVIA Centaur BNP; Bayer AG, Leverkusen, Germany) and a Boston Heart Failure Criteria score of at least 8 (Appendix 1). These criteria were chosen because they could be applied in a uniform, previously validated manner [6,7]. In the interest of collecting pretreatment baseline data, patients who had a score of at least 8 before reviewing the chest radiograph and BNP results were monitored. Patients were excluded if they were given an admission or discharge diagnosis other than HF, and the final discharge diagnosis was used to determine the presence of HF.

The stable HF group was enrolled from our outpatient HF clinic (?600 visits annually). Patients were enrolled if they were at their clinical baseline and did not have medication changes.

Exclusion criteria included factors that could alter microvascular oxygen dynamics: temperature less than 35?C or greater than 38?C, severe peripheral vascular

disease, sepsis, Active hemorrhage, or acute coronary syndrome.

Once consented, patients had tissue hemoglobin satura- tion (StO2) measured using a differential absorption spectrometer (O2C Monitor; LEA, Inc, Gie?en, Germany), which uses a white light source with filters to determine the ratio of oxy- and deoxyhemoglobin [8] within a volume of tissue containing arterial, capillary, and venous vessels. Direct Noninvasive measurement of the arteriovenous oxygen saturation difference to determine the OERM is not possible. However, a related surrogate is the arterial to tissue difference given by SaO2 – StO2, in which SaO2 is pulse oximetry-measured arterial hemoglobin oxygen content. For commonly accepted values of these volume fractions, Farterial = 0.1, Fcapillary = 0.2, and Fvenous = 0.7 [9], OERM can be calculated by OERM = (SaO2 – StO2)/0.8*SaO2.

The StO2 was measured on the palmar crease with the O2C Monitor probe taped into position (Fig. 1), which takes measurements once per second. From this, 10-minute average was used for analysis. bedside monitor blood pressure and pulse oximetry were measured twice and averaged during the same interval. Pulse oximetry was measured on the same hand as the StO2 measurement, whereas blood pressure was measured in the contralateral arm to prevent interruptions in blood flow during StO2. Serum hemoglobin and BNP measurements, if completed in the clinical evaluation, were recorded. Decompensated patients had OERM and mean arterial pressure (MAP) measurements repeated 3 hours after treatment initiation.

Significant cardiac comorbidities were recorded along with sex, age, and ethnicity. The etiology of HF (preserved

Fig. 1 The O2C Monitor percutaneous probe in position on the hypothenar eminence.

Age, y (95% CI)

56.1 (51.8-60.4)

60.7 (57.1-64.3)




20 (44.4)

20 (43.5)



25 (55.6)

26 (56.5)

African American

29 (64.4)

39 (84.5)



14 (31.1)

6 (13.4)


2 (0.02)

1 (2.1)


13 (28.9%)

14 (30.4%)



38 (84.4%)

46 (100%)

b.01 ?

High cholesterol

21 (46.7%)

31 (67.4%)


Coronary artery disease

23 (51.1%)

32 (69.6%)


Hemoglobin, g/dL (95% CI)

13.0 (12.6-13.5)

12.5 (12.0-13.0)


EF, % (95% CI)

35.3 (30.4-40.1)

30.7 (26.2-35.2)


HF etiology


15 (33.3%)

8 (17.4%)



30 (66.7%)

38 (82.6%)

MAP, mm Hg (95% CI)

90.3 (85.7-94.9)

Pre-Tx: 110.4 (102.6-118.2))

Post-Tx: 96.7 (90.8-101.8)

b.01 ?

b.01 ?


40 (88.9)

43 (93.4)



31 (68.9)

27 (58.7)



45 (100)

3 (11.1)


18 (66.7)


6 (22.2)


1 (2.2)

9 (19.6)

b.01 ?


1 (100)

3 (33.3)


6 (66.6)

Tx indicates treatment. PO indicates per os.

* P b .05.

vs reduced ejection fraction [EF], with an EF b50% considered abnormal) was determined from subsequent inPatient evaluation for the decompensated group and from record review for the stable group. During ED treatment, the medication dosage and method of delivery were recorded.

To assess HF severity in a uniform, quantitative manner, 2 Visual Analogue Scale tools were administered at each monitoring session (Appendix 2). The first VAS asked patients to rate their current degree of dyspnea and level of activity, ranging from asymptomatic to severe distress, using a 100-mm scale (0 = no difficulty; 100 = severe difficulty). The VAS was completed by the investigators and research personnel. To ensure uniform scoring, research personnel first observed the investigator VAS administration process and then were subsequently observed before independently assessing

patients. The second VAS, completed by research personnel, assessed the degree of observed patient diaphoresis and dyspnea using a 100-mm scale (0 = no obvious diaphoresis or dyspnea; 100 = severe dyspnea and diaphoresis).

To determine if pre- and posttreatment OERM during ED treatment changed over time or differed from stable HF patients, a repeated-measures analysis of variance (SAS version 9.2; SAS, Inc, Cary, NC) was used with an unstructured variance-covariance structure, reported with

Table 1

Patient demographics, comorbidities, and characteristics








Table 2 The results of the repeated-measures analysis of variance model for OERM between the stable (clinic), ED pretreatment, and ED posttreatment groups


Estimate (SE)


t value



0.649 (0.072)




ED pre-Tx

0.920 (0.072)




Fig. 2 Distribution and box-and-whisker plots of the stable and

ED post-Tx

0.751 (0.057)




the decompensated HF pretreatment and posttreatment groups’


Fig. 3 The OERM of the stable and the decompensated HF pretreatment and posttreatment groups. Tx indicates treatment. Error bars are standard error.

standard error (SE). Simulation results suggested that for an ? of .05 and a minimum power of 80%, a sample size of 45 patients per group was required. Secondary analysis determined if patient characteristics differed between the stable and decompensated groups using ?2 testing (nominal data) or a Student t test (categorical data).

Data distribution for continuous variables was analyzed with a normal quantile plot and, if found to be normally distributed, was reported as means +- 95% confidence intervals (CIs). Frequency analysis was done for patient comorbidities, sex, race, HF etiology, and medications, and reported as percentages. Median values with 25th and 75th percentiles were also reported.


Ninety-six patients were enrolled. Three decompensated patients later had non-HF diagnoses and 2 had incomplete data, leaving 45 stable and 46 decompensated patients for analysis. The stable and decompensated groups had similar demographics, except for increased prevalence of hyperten- sion (P b .0l) and hypercholesterolemia (P = .05) and reduced EF (P = .05) in the decompensated group. Mean arterial pressure was also higher in the decompensated group (Table 1). With the exception of Vasoactive medications, the Treatment regimens did not significantly differ. Continuous data appeared to be normally distributed.

Whereas the pretreatment OERM (Table 2) differed from the stable patient OERM (P b .01), the posttreatment OERM (Figs. 2 and 3) was not different from the stable patient OERM (P = .27). The stable patient MAP was significantly different from the pretreatment and posttreatment ED measurements (P b .01 for both).

Fig. 4 A, Distribution and box-and-whisker plots of the stable and the decompensated HF pretreatment and posttreatment groups’ patient VASs (millimeters). B, Distribution and box-and-whisker plots of the stable and the decompensated HF pretreatment and posttreatment groups’ observer VASs (millimeters).

The decompensated group serum BNP was 1497 ng/dL (95% CI, 1098-1896) and had no stable group comparison. The mean time from pre- to the posttreatment monitoring in the decompensated group was 150 +- 126 minutes, and inpatient length of stay was 5.4 +- 5.2 days.

The stable patient-scored VAS (Table 3) significantly differed from the pretreatment (P b .01) and posttreatment ED patient VAS (P b .01), and the patient-scored VAS decreased after ED treatment (P b .01). Stable patients had a significantly lower observer-scored VAS than the ED patients both at pretreatment (P b .01) and posttreatment (P = .01) (Fig. 4).


Aside from serum BNP, HF assessment in the ED setting has not materially changed in 50 years. Physical examination findings, vital signs, chest radiographs, [10] urine output, and Patient symptoms have poor accuracy in determining HF severity and response to treatment [1,11]. Although diagnosing

Table 3 Patient and observer VAS scores and SE for clinic and ED pretreatment and posttreatment groups


Patient VAS



t value


Observer VAS



t value



15.2 (5.6)




50.1 (4.5)




ED pre-Tx

125.2 (5.8)




28.0 (4.0)




ED post-Tx

84.0 (8.0)




7.4 (4.3)




* Denotes statistical significance less than 0.05.

HF has been improved by measuring serum BNP [12], it is only accurate for guiding treatment when high or low, as intermediate levels have less utility [4], particularly in those with chronic HF; and the utility of BNP to guide treatment is unclear [13,14]. This heterogeneity in assessment results in the inability in an individual patient to determine whether the primary problem is volume overload with adequate perfusion or, at the other end of the spectrum, inadequate tissue delivery of oxygen.

Differential absorption spectroscopy is a reliable technique that filters white light for wavelengths between 500 and 650 nm to determine the ratio of oxy- and deoxyhemoglobin within tissue 1 to2 mm below the skin surface [8]. The OERM derived from this measurement is a reflection of the balance between tissue oxygen delivery and oxygen consumption. Reductions in oxygen delivery are reflected as an increased OERM as tissues extract a greater proportion of oxygen to meet metabolic needs. In the setting of HF, the OERM represents tissue oxygen consumption in peripheral tissue that is subject to the vasoconstriction, endothelial dysfunction, diminished cardiac output, and fluid overload [15]. The directly measured StO2 value itself has been investigated in the outpatient HF population [16] and in the acutely decompensated ED population [17], with promising results. The advantage of OERM measurement is the ability to take into account arterial blood oxygen content entering the tissue, which is important because hypoxemia often results from severe HF.

We found that microvascular oxygen utilization abnor- malities exist in acutely decompensated HF ED patients when compared with stable outpatient HF patients. Peripheral tissue oxygen extraction was highest before ED treatment, which then decreased after treatment, approaching values found in the stable HF population. Physiologically, the oxygen extraction ratio is a measure of how much oxygen has been extracted by peripheral tissue in HF. The wide variation we found likely reflects the severity of the disease and/or the ability of individual patients to compensate for decreased tissue perfusion. Based on the degree of variation in the OERM measure, an individual absolute OERM value may not be as important as the relative change in the value during treatment. The elevated pretreatment values likely represent increased extraction due to decreased tissue oxygen delivery from the HF decompensation.

The decompensated and stable groups were similar in terms of age, sex, and ethnicity. Because serum Hemoglobin levels were similar between the 2 groups, the difference between oxygen extraction are likely not from differences in erythrocyte concentration. Although not statistically signif- icant, the stable group had a higher incidence of preserved EF HF, although measured EF was similar.

The need for an accurate guide to HF treatment, particularly in the ED setting, has become more pressing because delay in HF treatment has been associated with increased in-hospital mortality [18] and earlier intervention positively impacts patient outcomes and costs [19]. The OERM is a reproducible,

noninvasive, quantitative measure of microvascular oxygen utilization that might fit this role.


Although the stable and decompensated groups’ demographics and comorbidities were similar, hyperten- sion was more prevalent in the decompensated group. This could have affected results, as hypertension can affect arterial and arteriole compliance, potentially impact- ing microvascular tissue perfusion. Mean arterial pressure and pulse oximetry were measured only twice during each monitoring period. Because, within a 10-minute period, there was very little StO2 variation (1%-2% standard deviation), we thought that continuous blood pressure and pulse oximetry measurement was not necessary and adequately reflected by the average of 2 measurements over the 10-minute period.

Although the goal reassessment time frame was within 180 minutes, this did not always occur, as a result of monitor, personnel, or patient unavailability for remonitoring. This could have introduced a time effect on OERM measurement. Some patients with stable HF had EFs used for analysis that were obtained up to 3 months before or after enrollment.

It is possible that EF changed during the time between the last EF determination and enrollment.

We did not control for medication regimens during treatment, although the stable and decompensated patients had a similar frequency of diuretics and nitrates. Patients received commonly used ED treatment of acutely decom- pensated HF and were monitored over a reasonable period for these interventions to take effect. Future studies will examine OERM as specific medications are used.

Although physical examination and symptoms are poor indicators of HF treatment response and represent a study limitation, they remain the noninvasive criterion standard for assessing treatment and response. We used the VAS to assess patient response to treatment. Although subjective, it has been used previously in the acutely decompensated HF population [7,20].

Our population had a high proportion of African Amer- icans, who may respond differently to HF therapy [21,22]. Because the Boston Heart Failure Criteria were validated in predominantly white HF patients [6], the accuracy of this scoring system may be limited in our population.


This preliminary study of the use of novel technology to assess HF indicates that OERM is increased in patients with acutely decompensated HF and decreases after treatment to values found in the stable HF population. More study is needed to determine its role in the assessment and management of HF in the ED.

Appendix 1. Boston inclusion criteria


  • Chest radiograph findings

4 Alveolar pulmonary edema

3 Interstitial pulmonary edema

3 Bilateral pleural effusion

3 Cardiothoracic ratio N0.50

2 Upper zone flow redistribution Total:

Grand total: (Note: Only a maximum of 4 points from each category allowed.)

Basilar crackles

If crackles auscultated more than basilar


3rd heart sound

If 91-110 beats per minute If N110 beats per minute

N6 cm H2O

N6 cm H2O plus hepatomegaly or edema

Chest examination 1




Heart rate

  • Physical examination findings



Jugular venous distention 2



Dyspnea at rest Orthopnea

Paroxysmal nocturnal dyspnea Dyspnea while walking on level area

Dyspnea while climbing stairs

  • Patient history 4





Appendix 2. Subject VAS

Patient: Please mark on the following scale how you feel:

1. Patient-reported dyspnea

0 mm

100 mm

“I cannot breathe at all.” 100 mm

“I am short of breath just sitting here.”

100 mm

Needs intubation 100 mm

Dripping with sweat

“I can breathe as I normally do.”

2. Patient-reported level of activity 0 mm

“I can move around as I normally do.”

Observer: Rate the following observations:

3. Observer-reported dyspnea:

0 mm

No respiratory distress

4. Observer-reported diaphoresis

0 mm

Skin is dry


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