One of the big advantages of animal over clinical research is that a range of physiologic conditions can be produced that enable testing of the performance of monitoring equipment to an extent that cannot be achieved in human subjects, and this statement could not be more pertinent than when applied to the measurement of cardiac output (CO).1,2 In this edition, Kutter et al.3 have performed an exemplary animal study that shows the differences among 4 common CO measurement methods that use either a pulmonary artery (PA) catheter or femoral arterial catheter. A modified Fick method using carbon dioxide (CO2) production, rather than oxygen uptake, was chosen as the reference standard. Their study results are of clinical interest because they compare the performance of several techniques that measure CO from either the pulmonary circulation (i.e., right heart) or the systemic circulation (i.e., left heart) during induced pulmonary hypertension. The pressures in the PA can be affected by acute lung injury and high CO states, and it is clearly important to know how reliable different monitoring techniques are under such circulatory conditions.
What makes Kutter et al.’s study of special note? They have comprehensively investigated the effects on standard clinical CO monitoring of 4 well-defined pressure-flow conditions affecting the pulmonary circulation. Their data collection, despite using a small number of subjects (i.e., 9 pigs), was sufficient to show significant differences in performance. The statistical methods, although daunting on first read, and analytical methods were robust and showed differences in precision (i.e., Bland-Altman and precision error) and trending ability (i.e., 4 quadrant concordance and polar plots).4,5 They also address a currently relevant clinical issue, the choice between PA catheter and transpulmonary thermodilution for CO measurement.6,7 The relevance of the pulmonary circulatory changes, and pulmonary hypertension in particular, lies with the use of these monitors in major surgery or critically ill patients.8
The choice of reference method for CO validation studies has become an issue of controversy in the literature, with the time-honored PA catheter giving way to Doppler-based methods such as transthoracic echocardiography and esophageal Doppler (CardioQ; Deltex Medical Ltd., Chichester, England).9,10 Transpulmonary thermodilution is another possible solution. None of these alternative reference methods has been fully validated. The clinical use of the PA catheter has been criticized because of patient safety issues and questionable precision.9,11 However, the experience from our group of using Arrow (Arrow Int.; Teleflex Medical, Reading, PA) and Edwards Swan-Ganz (Edwards Lifesciences, Irvine, CA) PA thermodilution catheters in vitro (i.e., bench test rig) and in vivo (i.e., anesthetized pig model) was that the PA thermodilution catheter itself was a very well-made and accurate device. Issues regarding its accuracy arise because of (1) user technique and dead-space effect, (2) mismatch of computer or monitor software, and (3) malposition of the catheter and its tip within the tubing of test rigs or blood vessels (i.e., PA).12,13 The latter may be relevant when pulmonary hypertension exists or is induced. Kutter et al. have turned the accuracy issue on its head by using a modified Fick method as their reference standard and comparing the different thermodilution modalities. In doing so, they provided valuable performance data. But how reliable was their reference method? They used the NICO 2 Respironics CO2 analyzer (Respironics Inc., Murrysville, PA) to measure CO2 production. The original NICO and partial CO2 rebreathing method released in the 1990s gained a poor reputation among clinicians and was never accepted clinically.14,15 Respironics’ modern-day CO2 analyzer does appear to be more reliable and did not measure CO.16 Instead, blood gas analyses were used to measure the mixed venous and arterial CO2, which were needed for their modified Fick CO equation.17 The Fick method has always been a gold standard in CO measurement research but has tended not to be used in anesthesia and critical care because of the logistic difficulties of performing the method in busy clinical settings. However, in the context of the present study, its use seems reasonable. The other issue not answered was what was the precision of their Fick method? It is needed if precision errors are to be standardized and used as criteria for acceptance.4
Kutter et al.’s data show that all 4 tested methods, such as PA catheter, transpulmonary thermodilution, continuous thermodilution, and arterial pressure wave analysis, detected high and low CO changes. However, whereas increases in PA pressure to 25 mm Hg caused no detectable CO changes, increases to 40 mm Hg were detected by all 4 methods except continuous thermodilution. Bland-Altman precision error was able to differentiate among the performances of the different CO methods. Most significant was the comparison between the PA catheter and transpulmonary thermodilution, which suggested that transpulmonary thermodilution was better. The Bland-Altman results (Table 2 in the study of Kutter et al.) repeatedly showed improved performance against the Fick reference method of the transpulmonary measurements (i.e., lower percentage errors) across all tested conditions. These outcomes were repeated in the trend analysis results that showed that the transpulmonary concordance rate of 100% was better than the PA catheter rate of 96%. Both rates were above the 92% threshold for good trending ability.5
What is concerning about Kutter et al.’s data is the poor results from both continuous CO methods. The continuous thermodilution catheter method had unacceptable precision errors when tested using high and low CO states and in particular the high PA pressure (i.e., 40 mm Hg) (Table 2 in the study of Kutter et al.). Furthermore, the concordance rate of 88% was poor (Table 3 in the study of Kutter et al.). Continuous thermodilution has a slow response time of 5 to 20 minutes, and one does have to wonder why people persist with using this technology for measuring CO changes. The arterial pulse contour method using the PiCCO system (Pulsion Medical Systems, Munich, Germany) was equally unreliable, but the limitations of pulse contour analysis CO are no surprise and very well documented.18
Kutter et al. also provide a series of half-moon polar plots. The value of these plots is that they show how well the 2 thermodilution methods, PA catheter and transpulmonary, track changes in CO relative to Fick with data points lying along the zero axis and within narrow limits of radial agreement (Fig. 3, A and B, right, in the study of Kutter et al.), whereas the continuous and pulse wave methods had data points that did not track changes in CO reliably and had significant negative direction offsets from the zero axis. Overall, the statistical analysis was comprehensive and well performed.
Transpulmonary thermodilution CO using the PiCCO system has recently been proposed as a safer alternative reference method to the PA catheter, and there are several published validation studies that support its use as an alternative method.6,19,20 Considering that invasive CO monitoring is used most widely in critically ill patients where lung injury, pulmonary hypertension, and high CO states are most prevalent, reliable scientific data such as Kutter et al.’s showing that the PA catheter is less reliable than the transpulmonary method in this setting is highly significant and raises the question as to whether transpulmonary thermodilution should become the accepted clinical standard. Certainly, the effects of pulmonary circulation changes on the performance of these CO monitors as Kutter et al. have shown need further consideration.
Name: Lester A. H. Critchley, MD, FFARCSI, FHKAM.
Contribution: This author helped in manuscript preparation.
Attestation: Lester A. H. Critchley approved the manuscript.
Name: Jie Zhang, MB BS.
Contribution: This author helped in manuscript preparation.
Attestation: Jie Zhang approved the manuscript.
This manuscript was handled by: Maxime Cannesson, MD, PhD
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