Impedance cardiography (electrical velocimetry) and transthoracic echocardiography for non-invasive cardiac output monitoring in pediatric intensive care patients: a prospective single-center observational study

This single-center observational study aimed to validate EV compared with TTE in pediatric intensive care patients with normal cardiac biventricular anatomy. LVSV was simultaneously measured by EV and TTE. Equivalence of EV and TTE was assumed if Bland–Altman analysis had bias <10% and mean percentage error (MPE) <30% regarding LVSV measurement by EV compared with TTE (H₀) [13].

An Aesculon® monitor (CE 0123; Osypka Medical, Berlin, Germany) was used to record EV. The electrode position of four RedDot® neonatal ECG radiolucent prewired monitoring electrodes (3M Health Care, Neuss, Germany) was chosen as recommended by the manufacturer. The analyzed heart beats were recorded simultaneously by TTE on the Aesculon® monitor. The signal that was generated by the Aesculon® monitor for EV LVSV measurements was accepted if the green signal quality bar indicated a reliable signal.

For echocardiography, either the GE Medical Systems Vivid 7 (CE 0470; GE Healthcare, Munich, Germany) or the GE Healthcare Technologies Logiq P5 (CE 0459; GE Healthcare) ultrasound machine was used. LVSV by TTE was calculated using two different methods [14],[15]. In one method, LVSV was calculated based on measurement of the flow velocity time integral (VTI) measured over the aortic valve (measured from an apical four-chamber view with angle correction, if necessary) multiplied by the area of the aortic valve:

where the aortic valve diameter was determined by triplicate measurements of the internal diameter of the aortic valve hinge points:

In the other method, LVSV was based on M-mode measurement in the long parasternal axis, using the internal algorithm of the echocardiography machine based on the Teichholz equation [16]. For these M-mode measurements, a single beat was simultaneously measured in triplicate by TTE and EV.

Three consecutive heart beats for VTI measurements or a single beat for the M-mode measurement were simultaneously recorded with the corresponding identical EV beats. All of the TTE measurements were performed by a single operator (MEB).

Pediatric and neonatal patients treated at the University Medical Center Hamburg–Eppendorf (UKE) in the pediatric and neonatal ICUs were eligible. This study was approved by the ethics committee of the Chamber of Physicians Hamburg, Germany. This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. National laws were observed. Parental written informed consent was obtained prior to data collection.

The distribution of data was graphically assessed. Right-skewed data were logarithmically transformed prior to statistical analysis. The intra-class correlation for repeated measurements on the same day in individual patients was high (97% for comparison of EV versus the LVSV measurement based on the VTI over the aortic valve (EVVTI), 98% for comparison of EV versus the LVSV determination by M-mode echocardiogram (EVMM)). Data were therefore combined into 285 measurement pairs (EV vs. TTE) by averaging the LVSV measured by each method in an individual patient, thus representing a single day of measurement in a single patient (n = 146 EVVTI combined data points, n = 139 EVMM combined data points). Agreement between the EV and TTE methods was assessed by means of Bland–Altman plots [17],[18]. The MPE was computed as:

where precision was defined as the two-standard-deviation method difference [13],[17],[19]. True precision for EV (TP_EV) was calculated based on the following equation [20],[21]:

A mixed-model analysis (analysis of covariance) was performed to identify the effects of persistent ductus arteriosus (PDA), persistent foramen ovale, the combination of PDA and persistent foramen ovale, non-invasive continuous positive airway pressure (CPAP) ventilation, any form of ventilation, use of catecholamines, outcome, body weight, secondary abdominal closure, sex, and heart rate on EV and TTE. Post-hoc power analysis was performed and the least significant change was calculated [20],[22]:

The trend-following characteristic over repeated measurements was determined using Kendall's coefficient of concordance. The statistical significance level was set to 0.05. SPSS version 20.0 (IBM, Armonk, NY, USA) was used for all statistical analyses.

To achieve a simultaneously paired LVSV measurement of identical heart beats by EV and TTE, the echocardiography used in the present study was only in a single plane rather than in two opposing planes. The precision of TTE in this study might therefore not have been as good as 30%, which has been reported in the literature [19]. However, the precision of TTE might have been better than the MPE of 36% reported in children for systems with blind Doppler probe positioning [34],[35]. The precision of TTE in this study was calculated as approximately 8%. Additionally, the precision of TTE was not homogeneous and depended on patient subgroups with lower precision, particularly in the PREM subgroup, contributing to higher bias and MPE in that subgroup.

Another limitation of the study may be due to variation in LVSV during the respiratory cycle. Our study used paired measurements irrespective of the respiratory cycle, and did not take into account that the variation in stroke volume was between 10 and 30% in most cases. In vigorously breathing neonates, the variation was as high as 40% (as indicated by the Aesculon® monitor). The variation in stroke volume during the respiratory cycle is a problem for any method of determining CO [26],[30],[36],[37]. Theoretically, variation in stroke volume should equally affect EV and TTE.

Previous studies have shown a significant effect of extravascular lung water on impedance cardiography CO measurements based on the Sramek–Bernstein equation compared with CO by thermodilution [33]. This implies that heterogenic patients with different amounts of extravascular lung water (as in this study) have heterogenic EV measurements, and this will affect comparison of EV and TTE.

To base goal-directed therapy on a monitoring tool such as EV CO measurement, the capacity of the applied method for determining a trend is important [20],[38] (that is, the ability of the method to detect a change in CO over time). Figure 3, which shows repeated measurements over time, demonstrates that the average direction of bias between EV and TTE remained positive or negative with repeated measurements. The high Kendall’s concordance mathematically supports this visual estimate of the constancy of the bias both for repetitive tests on the same day and on different days. By increasing the sampling interval with more measurements or more heart beats, the MPE between the two compared methods will become less (that is, precision will improve) [20],[22]. The least significant change is defined as the minimum change that needs to be measured by a device to recognize a real change [22]. According to the equation for calculating the least significant change, the minimum percentage of LVSV change detected by EV in this study was 11.3% (sampling interval of three heart beats). After five measurement cycles (equivalent to 15 heart beats), the least significant change for EV would theoretically [22] become 5%. This implies that at a heart rate of 60 beats/minute EV would theoretically be able to detect a 5% change in LVSV within 15 seconds of averaged measurement. This short time response to a relatively small change in LVSV implies good tracking properties of the EV method [38]. Other continuous CO monitoring devices, including non-invasive devices (for example, continuous Doppler-based systems) [34],[35] and invasive devices (for example, transpulmonary thermodilution methods combined with pulse contour analysis) [11],[12], normally average multiple cardiac cycles for more accurate continuous monitoring. Because EV is a non-invasive and continuously applicable method, combined measurement cycles averaging LVSV and CO over multiple heart beats are technically possible. This averaging would also equalize variation in stroke volume during the respiratory cycle. EV therefore appears to be suitable for monitoring trends. The advantages of non-invasiveness and continuity of EV, with a low bias compared with TTE, may outweigh the relatively low precision of this method.

In summary, LVSV measurements by EV and TTE were not different in pediatric intensive care patients if LVSV was determined by TTE using transaortic flow (EVVTI). This finding was observed for the whole cohort and for the subgroups OTX, NEURO, and SEPSIS, but not for the PREM subgroup. This equivalence could not be demonstrated because of a high MPE for EV and TTE if LVSV was determined by M-mode (EVMM), except in the OTX and NEURO subgroups. The poorer agreement between EV and TTE in the PREM subgroup may be related to the fact that nasal CPAP was the main parameter that affected differences between the methods. Because the average direction of bias between EV and TTE with repeated measurements in the same patients remained constant, EV appears to be a suitable method for following trends in CO.