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Precision and Accuracy of Non Invasive Hemoglobin Measurements during Pregnancy

Jul. 15, 2012

Precision and Accuracy of Non Invasive Hemoglobin Measurements during Pregnancy
Eran Hadar, Oded Raban, Tal Bouganim, Kinneret Tenenbaum-Gavish, Moshe Hod
Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva
and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Abstract:
The NBM-200 is a novel device allowing non invasive hemoglobin measurement. The system is based on occlusion spectroscopy technology in the red/near-infrared range. At the core of this technology is the production of a new bio-physical signal, resulting from temporarily occluding the blood flow in the measurement site. The measurement is performed using an annular, multi-wavelength probe with pneumatically operated cuffs, with which an over-systolic pressure is produced at the finger base.

Methods: OrSense NBM200 was tested during the years 2011-2012 in a population of pregnant women. Upon receipt of informed consent, two non-invasive Hemoglobin measurements were performed on the right and left thumbs of each subject. Reference hemoglobin values were obtained from venous blood samples drawn at the same time of the non invasive measurement. Blood Hemoglobin was evaluated on an LH-750 Beckman Coulter counter, acting as the reference “gold standard”.

Results: A total of 126 data pairs were obtained in the trial from 63 women. The mean error (bias) of the NBM200 readings compared to the reference was 0.1 g/dL and the accuracy, defined as the standard deviation of error, was 0.86 g/dL. A Bland-Altman comparison of the NBM200 versus the Coulter device shows that the 95% limits of agreement is -1.59 to 1.79g/dL.

Conclusion Our study demonstrates a good correlation between reference blood hemoglobin and non invasive hemoglobin measurements. The NBM-200 can accurately assess hemoglobin levels, in a non-invasive fashion, during pregnancy.

Introduction:
Gestational anemia and obstetrical hemorrhage are associated with adverse pregnancy outcome, both maternal and fetal (1-4). In such settings, as well as other pregnancy related scenarios, a clinical perspective aided by measurement of blood hemoglobin level is an important assessment, with major impact on therapeutic decisions.

There are several methods to estimate the amount of blood loss. The most widely used, and without a doubt the simplest one, is a clinical estimation using a combination of vital signs and visual estimation of the amount of bloodshed. However, the estimated sensitivity and specificity for this method are 50% and 92%, respectively, with a clear trend for underestimation (5). Another, perhaps more accurate method, although much less practical, is a direct measurement of lost blood. This is achieved by collecting lost blood in designated containers and/or the estimation of the number and weight of blood-soaked swabs, during surgical procedures. Laboratory methods, e.g. levels of hematocrit and hemoglobin, are extremely helpful. However, the process up to final results is time consuming and not universally accessible (6). Laboratory based hemoglobin measurements are invasive, require transport of samples and may elicit occasional exposure to biohazard. All this taken into account, laboratory based hemoglobin measurements, may at times, lead to delay in recognition of anemia and institution of therapy. Other than that, the invasive measurement is more painful and less comfortable for the women being examined.
Therefore, an easy to use, non invasive and accurate method to measure hemoglobin and/or hematocrit is of importance. Such a method may allow early recognition and continuous monitoring of the amount of blood loss (7). Also, it will be available in remote, low resource regions. Due to its rapid availability, non invasive approach and being less painful, such a system is expected to increase patient’s compliance and improve follow-up.
The OrSense NBM200 is a non-invasive hemoglobin test device. The NBM200 device is based on occlusion spectroscopy technology in the red/near-infrared range (8,9). At thecore of this technology is the generation of a new bio-physical signal resulting from temporarily occluding the blood flow in the measurement site. The measurement is performed by using an annular, multi-wavelength probe with pneumatically operated cuffs, which generate an over-systolic pressure at the finger base. The monitor is user friendly with an easy to use interface. The device is targeted for use by caregivers in hospitals, clinics, blood donation centers, large population screening and home monitoring for the application of anemia detection and hemorrhage monitoring. The device enables continuous and spot measurement or monitoring of hemoglobin, as well as oxygen saturation with a possible addition of glucose and more anylates in the future.
Several non invasive hemoglobin measurement devices exist commercially, and have been previously studied with numerous results available in the literature. The most widely studied device is the Masimo Radical-7 monitor (10-17), which is based on multiwavelength pulse co-oximeter technology. Other devices studied are the Masimo pronto-7 monitor (18) and the OrSense NBM200MP (18). In contrast to the Masimo devices, the NBM-200 uses differential light absorption before and after blood flow obstruction in the finger to determine hemoglobin level non-invasively.
Thus, we aimed to test the accuracy of the NBM200 in measuring hemoglobin, in a population of pregnant women. We hypothesized that the device’s non-invasive hemoglobin readings will be accurate with an acceptable difference compared to currently available invasive methods.

Methods:
The study was designed as a prospective cohort study, aimed to assess the OrSense NBM200, a non-invasive hemoglobin test system. The device was tested during the years 2011-2012 in the Women’s hospital at the Rabin Medical Center in Petah Tikva, Israel. The study was approved by the institutional review board prior to its initiation.

Device Description (Figure 1): The OrSense NBM200 (OrSense, Nes-Ziona, Israel) measurement system is a non-invasive finger blood analytes monitor intended for use in clinical investigation. The monitor system is a microprocessor-based with resident medical software library line-fed portable medical instrument, comprised of electronic and display circuits box and the finger sensor. The finger-based sensor probe consists of the following elements: 1) Light source comprised of 10 spectrally stabilized emitters (LED’s) in wavelength ranging from 600nm to 950 nm. 2) Photo-detector. 3) An air cuff pneumatic occluder for application of over-systolic pressure to the finger during the spectroscopic measurement. 4) Extension connecting cable.

Study Population: Pregnant women, subject to a planned routine blood testing, were asked to participate in the study. Following informed consent, willing participants were screened for inclusion/exclusion criteria. Only those without any exclusion criteria, who gave written informed consent and which are intended to undergo a routine blood count as part of their planned management and follow up, were included in the study. The inclusion criteria for the study were: 1) Pregnant women; 2) age ≥ 18 years; 3) routine blood count is planned. The exclusion criteria were as follows: 1) Age < 18 years ; 2) Significant deformity, degenerative changes or edema of the thumb or index fingers; 4) Localized infection, ulceration or skin breaks involving the fingers; 5) Peripheral body temperature <36.0˚C; 6) Vascular disease or Raynaud’s phenomenon affecting the fingers.

Study Protocol: Reference hemoglobin values were obtained from a venous blood sample and evaluated on a Beckman Coulter LH 750 counter. As soon as possible after taking the blood count (and up to 1 hour), the NBM200 sensor was placed on the subject's thumb and the non invasive reading was then performed. For each woman participating in the study, two non-invasive hemoglobin measurements were performed on the right and left thumbs. The duration of the reading is approximately 100 seconds. All reference measurement values were recorded and documented as mandated, and all treatments and medical decisions, recommendations and follow up were based on the blood count alone. The results from the NBM200 sensor were not recorded in the patient's chart, and remained blinded to the caregivers.

Data Collection: Clinical and demographic information, including past medical history, obstetrical & gynecological history as well as the cause for admission and clinical procedure intended were collected and recorded. The date and time of the routine blood count, as well as the time of the non-invasive test were also documented.

Data Analysis: The accuracy of NBM-200 as compared to standard hemoglobin measurement was studied using Bland-Altman analysis of bias and precision. The Bland–Altman analysis was applied for calculating bias (Error), defined as the mean difference between both methods, and accuracy defined as the standard deviation of the error as well as limit of agreements which is the range in which 95% of the differences between the two methods lie (19).

Results:
A total of 126 data pairs were obtained during the trial period from 63 pregnant women. Reference hemoglobin values were in the range 6.9 - 13.9 g/dL, and the values obtained by the NBM200 device were in the range of 7.7 - 14 g/dL.

Compliance: There was full compliance to the measurements by all women approached to participate in the study. No adverse events were reported during the evaluation by the NBM200, and all measurements were well tolerated by the participating women. In all cases, we were able to obtain full evaluation of both measurements (left and right thumb), for the full length of the examination, with no woman asking to terminate the measurement during its performance.

Demographics (Table 1): The demographic characteristics of the participating women are summarized in table 1.

Hemoglobin Level Concordance: The mean error (bias) of the NBM200 readings compared to the reference was 0.1 g/dL. The accuracy, defined as the standard deviation of error, was 0.86 g/dL. The correlation was 0.82 and the mean absolute error was 0.71 g/dL. A scatter plot of the NBM200 Hemoglobin vs. reference Hemoglobin values is shown in figure 2. A Bland-Altman comparison of the NBM with the reference Coulter device is presented in figure 3. The range [-1.59, 1.79] g/dL represents the 95% limits of agreement, which is the range within which most differences between the two measurement methods lies.

Discussion:
Measurement of blood hemoglobin levels is a day to day practice in most medical practices. Applying a non-invasive point-of care device facilitates faster results, with less pain and discomfort for the examinee. In this study we evaluated the performance and accuracy of the NBM200 device. Concisely, we have demonstrated in a population of 63 pregnant women, undergoing 126 non invasive measurements that the NBM200 non invasive hemoglobin measurement is acceptably accurate compared to traditional invasive methods with a mean error of 0.1 g/dL, absolute error of 0.71 g/dL and an accuracy of 0.86 g/dL (Figure 2). The limits of agreement were found to be in the range of -1.59 to 1.79 g/dL (Figure 3).
Gayat et al. (18) in a recently published study evaluated the NBM-200MP, a continuous version of NBM200, and the Pronto-7 monitor versus usual blood sample measurements in the setting of an emergency room. The results for the NBM200MP device were obtained form 297 patients and they report a mean difference of 0.21 g/dL and limits of agreement in the range of -3.01 to 3.42 g/dL. Our current data show better performance and concordance, with a smaller error of 0.1 g/dL and a narrower limit of agreement, -1.59 to 1.79 g/dL, suggesting a good probability of clinical use. It is important to note that the NBM-200MP tested in their trial is a bedside monitor, intended for continuous measurement of Hemoglobin, and its performance is not optimal for short spot testing as in our study.
Other than the NBM-200, previous studies have focused on other devices, mainly utilizing Co-Oximeter techniques (10-18). Results published thus far, have shown inconsistent results with a wide variation in reported biases for the non invasive measurements ranging from -1.7g/dL to 1.8g/dL. All of these studies (10-17) evaluated the Radical-7 monitor, which is a hospital-use monitor that continuously measures Oxygen saturation, Hemoglobin and other blood anylates. The Pronto7 is a spot device based on a similar technology as for the Pronto-7 monitor (18).

The rate of impossible measurement was the lowest in our study as all 126 measurements were successfully made. Previous studies have reported higher failure rates in other devices - 2.5% (18) and 8% (16).
As for any laboratory procedure bias may occur, so it is important to emphasize that even gold standard techniques may have an inter- and intra-device variation. The acceptable error considered in the literature ranges form 1-1.5g/dl. Our data suggests that the NBM200 is well within this range (20). Our study is the second to evaluate the NBM200 device and the first to do so in a selected population of pregnant women. The main limitation of our study is the small sample size, thus further studies are needed in a larger population, and a wider range of hemoglobin values.

Conclusion:
Our study demonstrates a good correlation between reference hemoglobin and noninvasive hemoglobin measurements. The NBM-200 can accurately assess hemoglobin levels, in a non-invasive fashion, during pregnancy. A noninvasive accurate hemoglobin evaluation may serve an important role in obstetrics, allowing easy, rapid and accessible evaluation of hemoglobin during pregnancy. It may play a crucial role in monitoring hemorrhage during and after labor.
Accordingly, a multicenter multinational study aimed to evaluate compliance and feasibility in rural areas of low income countries of the developing world, will be carried out in the near future.

References:
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