Cardiac output estimation by multi-beat analysis of the radial arterial blood pressure waveform versus intermittent pulmonary artery thermodilution: a method comparison study in patients treated in the intensive care unit after off-pump coronary artery bypass surgery

Cardiac output (CO)—as a main determinant of oxygen delivery—is a key hemodynamic variable to guide therapy in critically ill patients with circulatory shock [1]. Invasive indicator dilution methods such as pulmonary artery thermodilution (PATD) [2] and transpulmonary thermodilution [3] remain the clinical reference methods to assess CO and novel minimally-invasive hemodynamic monitoring tools should be validated against these invasive reference methods [4‐6]. Invasive uncalibrated pulse wave analysis requiring only an arterial catheter is increasingly used as a minimally invasive method for stroke volume—and thus CO—estimation in surgical and critically ill patients [5‐7]. The term pulse wave analysis comprises several markedly different approaches and algorithms to estimate stroke volume by analyzing the arterial blood pressure waveform [8, 9]. As a main advantage, pulse wave analysis enables CO to be estimated continuously. It is therefore recommended for real-time CO estimation during functional tests of fluid responsiveness such as the passive leg raising [10] or fluid challenge test [11].

Multi-beat analysis is a novel method to estimate stroke volume by mathematically analyzing the radial blood pressure waveform over time scales greater than a single cardiac cycle without external calibration. This enables beat-to-beat waveform variations to be considered and effects of pulse wave reflections to be minimized; eventually, by analyzing the waveform over several cardiac cycles, the multi-beat analysis method aims to identify the pure exponential pressure decay of the arterial blood pressure waveform without confounding wave reflections in the periphery of the arterial vessel tree and estimates stroke volume using a proprietary formula and biometric data [12, 13]. Based on experimental [13] and retrospective [12, 14, 15] pilot studies Retia Medical (Valhalla, NY, USA) developed a commercially available bedside CO monitor using multi-beat analysis—the Argos monitor—that was recently cleared by the US Food and Drug Administration (FDA). In this clinical method comparison study, we compared CO estimations by multi-beat analysis of the radial arterial blood pressure waveform (Argos monitor) to CO measured by intermittent PATD in adult patients treated in the intensive care unit (ICU) after off-pump coronary artery bypass surgery (OPCAB).

A total of 284 paired PATD-CO and MBA-CO measurements in 42 patients were recorded. Two patients had to be excluded because of malposition of the PAC and one patient was excluded because of excess motion artifacts of the blood pressure waveform. 106 segments were excluded because of inappropriate damping properties or artifacts of the blood pressure waveform. We included 167 paired CO values of 31 patients in the final analysis.

Basic patient characteristics are shown in Table 1. The relation and within-subject correlation of PATD-CO and MBA-CO is shown in Fig. 1. Mean PATD-CO and MBA-CO were 5.30 ± 1.22 L/min and 5.55 ± 1.82 L/min, respectively. Bland–Altman analysis revealed a mean of the differences between PATD-CO and MBA-CO of 0.08 ± 1.10 L/min (95% limits of agreement: − 2.13 L/min to + 2.29 L/min) (Fig. 2). The percentage error was 40.7%. Four-quadrant plot analysis is shown in Fig. 3. The concordance between changes in PATD-CO and MBA-CO was 88%.

In this method comparison study, CO estimations by multi-beat analysis of the radial arterial blood pressure waveform (Argos monitor) showed reasonable agreement and trending ability compared with CO measured by intermittent PATD in adult patients treated in the ICU after OPCAB.

This is the first prospective method comparison study evaluating the CO measurement performance of the novel multi-beat analysis algorithm now included in the recently FDA-cleared Argos monitor in comparison with intermittent PATD—the clinical reference method—in patients treated in the ICU after cardiac surgery. Previous studies investigated former versions of the multi-beat analysis algorithm in comparison with experimental gold standard CO measurements (aortic flow probe) in animals [13] and retrospectively in comparison with thermodilution CO measurements in 15 [12] and 169 [15] patients from a freely accessible ICU database. These previous studies showed promising results with regard to the CO measurement performance of the multi-beat analysis method. However, in these previous studies, the agreement and trending ability of the multi-beat analysis method with the reference method were assessed using calibrated multi-beat analysis-derived CO estimates, i.e., the CO estimates were calibrated to the reference CO values and multi-beat analysis was used as a calibrated pulse wave analysis method [8, 9]. In contrast, in our study, we used multi-beat analysis as a—so-called—”uncalibrated” pulse wave analysis method only using arterial blood pressure waveform data and biometric information to estimate CO [8, 9]. Therefore, our findings are not indiscriminately comparable to results of these previous studies.

In 2010, Peyton and Chong [22] published an extensive meta-analysis on minimally-invasive methods for CO estimation in surgical and ICU patients. For pulse wave analysis methods, this meta-analysis yielded an overall pooled mean of the differences of 0.00 L/min (± 95% confidence interval, ± 0.09 L/min), a pooled standard deviation of the differences between paired measurements of 1.22 L/min, and a pooled percentage error of 41.3% (± 95% confidence interval, ± 2.7%). Of note is that this meta-analysis included both uncalibrated and calibrated pulse wave analysis methods. Compared with these pooled results our study investigating uncalibrated multi-beat analysis revealed a slightly lower standard deviation of the mean of the differences and percentage error.

Four-quadrant plot analysis and the concordance rate are used to describe the ability of a test method to adequately and timely detect changes in a hemodynamic variable measured with a reference method. In our study, the concordance rate between changes in MBA-CO and PATD-CO (88%) reflects good trending ability of multi-beat analysis. The concordance rate is markedly higher than the ones observed in recent studies comparing the latest version of an established pulse wave analysis algorithm (FloTrac; Edwards Lifesciences, Irvine; CA, USA) with pulmonary artery thermodilution in patients having cardiac surgery using cardiopulmonary bypass [23, 24].

In general, irrespective of the specific method used, a key prerequisite for pulse wave analysis to provide accurate and reliable estimations of hemodynamic variables is an optimal signal quality of the arterial blood pressure waveform. Artifacts in the arterial blood pressure waveform can be caused by movement or by inappropriate damping properties (underdamping/resonance artifacts or overdamping) of the monitoring system consisting of the arterial catheter, a fluid-filled tubing system, and a pressure transducer [16, 25‐27]. In accordance with our study, it has been demonstrated that underdamping/resonance artifacts occur in about one-third of cardiovascular patients in the operating room or ICU [26, 27]. Underdamping/resonance artifacts can result in a marked overestimation of systolic arterial blood pressure and incorrect estimation of pulse wave analysis-derived hemodynamic variables such as stroke volume, CO, and pulse pressure variation [26, 27]. Therefore, during routine clinical care, we repeatedly perform “fast-flush tests” [16, 25] to evaluate the dynamic response of the arterial blood pressure monitoring system. To be able to objectively describe the actual measurement performance of a pulse wave analysis method in comparison with a reference method in a method comparison study it is essential to only include impeccable arterial blood pressure waveforms not disturbed by artifacts or inappropriate damping properties of the arterial catheter/tubing system. We, therefore, carefully checked the quality of the recorded arterial blood pressure waveforms and excluded waveform segments that were likely to be altered by inappropriate damping properties (underdamping/resonance or overdamping) and other artifacts. On the one hand, excluding artifactual waveforms is a key prerequisite to draw meaningful conclusions from method comparison studies on pulse wave analysis algorithms. On the other hand, excluding waveforms might increase the risk for selection bias and limit the generalizability of our findings to routine clinical conditions.

Another limitation of our study is that we did not use the multi-beat analysis monitor at the bedside, but recorded arterial waveform segments during routine care and later performed off-line analysis to estimate MBA-CO. In addition, because this was a single center study including patients after OPCAB surgery our results might not be generalizable to other settings or patient collectives. Further, our study setting was not designed to evaluate the trending ability of multi-beat analysis because the patients were in a relatively stable hemodynamic state and no CO-changing interventions were performed between study measurements. This resulted in a limited number of eligible observations for tending analysis.

CO estimations by multi-beat analysis of the radial arterial blood pressure waveform (Argos monitor) show reasonable agreement compared with CO measured by intermittent PATD in adult patients treated in the ICU after off-pump coronary artery bypass surgery (OPCAB). For further assessment of the trending ability additional studies are needed.