A prospective study to evaluate the accuracy of pulse power analysis to monitor cardiac output in critically ill patients

The measurement of cardiac output is an important component of the management of critically ill haemodynamically unstable patients[1, 2]. In recent years there has been increasing emphasis towards the less invasive or minimally- invasive monitoring tools [3‐10]. There are a number of commercially available monitors that measure cardiac output from an intra-arterial pressure line. These utilize different algorithms to relate changes in arterial pressure to changes in stroke volume and thus cardiac output [1, 2, 4, 8, 9, 11]. To date the most accepted of these devices have required an independent form of validation or calibration of cardiac output. This calibration remains valid so long as there are no significant changes in the haemodynamic status of the patients. It is unclear as to when and under what conditions this re-calibration should be performed.

The LiDCOplus monitor (LiDCO, Cambridge, UK) is a device that combines a pulse power algorithm (PulseCO) with an independent form of calibrating the pulse power algorithm via lithium dilution (LiDCO) [3]. This device has been validated in a number of different clinical and veterinary conditions. To our knowledge there are no data showing how well the algorithm maintains its accuracy during an eight hour interval free of calibration in a mixed (medical/surgical) adult intensive care population of critically ill patients. This study, therefore seeks to investigate the duration that the two methods remain sufficiently similar to be acceptable for clinical use.

Fourteen patients were enrolled into the study. Six of these patients were male and eight female. They had a median age of 67.5 (29–76) years, a median height of 1.66 (1.6–1.73) m and a median weight of 67 (58–102) kg. Five of the patients were post surgery and all were critically ill from a number of different aetiologies [Table 1]. Eight patients had multiple organ failure due to sepsis (6 medical, 2 surgical). The remaining six patients had acute heart failure (3 medical, 2 post partum, 1 surgical). In all fourteen patients measurements were available at baseline, 1 hour, 2 hours and 4 hours. In two patients data at eight hours were unavailable due to clinical priorities meaning the patients had had to be removed from the study [Table 2]. All the measurements were suitable for analysis. A total number of 54 pairs of data were available at the end of data collection.

The baseline data show a large range of cardiac outputs (LiDCO from 2.8 to 18.3 L/min) with a median cardiac output of 7.5 (5.1 to 9.0) L/min. The median heart rate was 104 (92–117) beats per minute, median arterial pressure 81 (72–93) mmHg and median central venous pressure 16 (12–19) mmHg [Table 2]. Seven patients were receiving a norepinephrine infusion to support the mean arterial pressure at the beginning and throughout the study period. Over the eight hour study period six of the fourteen patients had changes in their cardiac output of greater than 15% from their baseline value [Table 2].

At baseline, the cardiac output of the PulseCO system was equalized with the independent form of measurement (the LiDCO) meaning that the two monitors displayed exactly the same number. This absolute value of cardiac output from the PulseCO system remained acceptable as compared to the LiDCO for the next four hours of the study. Data for PulseCO and LiDCO at 1, 2 and 4 hours demonstrated an acceptable levels of bias and limits of agreement for the first four hours of the study, however at eight hours following calibration the PulseCO device had a percentage error that was outside of the acceptable range [Figure 1]. After one hour of study, the bias and limits of agreement between PulseCO and LiDCO were -0.3 ± 2.3 L/min with a percentage error of 29%, at two hours 0.1 ± 1.9 (22%), at four hours -0.1 ± 2.2 (28%) and at eight hours 0.2 ± 2.2 (36%) [Table 3].

The PulseCO system utilizes a pulse power algorithm to track changes in cardiac output from a baseline value. It is therefore important to also assess whether the changes in cardiac output between the two devices were of similar direction and magnitude. In this study there were significant agreements between the two techniques of detecting changes in cardiac output for the first four hours following calibration. This is evidenced from the significant correlation between percentage changes in the cardiac output from the preceding time point as measured by the PulseCO when compared to changes as measured by the LiDCO method (r² 0.46–0.76, p < 0.006). At eight hours the changes in cardiac output were not significantly correlated between the two devices [Figure 2]. The bias and limits of agreement for the percentage changes in the cardiac outputs between the two measurements were as follows: at one hour -3.5 ± 20%, at two hours 5.6 ± 24%, at four hours -0.4 ± 25% and at eight hours 1.4 ± 43% [Figure 2].

The separate plots of PulseCo and LiDCO against time for each patient [Figure 4] show how the two techniques track cardiac output. The graphs show that for the majority of patients the magnitude and direction of change in cardiac output is similar indicating that the two devices track cardiac output appropriately. In a few patients, this relationship is not so good, and this partly explains the percentage error for the limits of agreement that are detailed above. Although the accuracy of cardiac output measured by the PulseCO system remained adequate for the first four hours of the study it is important to recognize that in individual patients the accuracy over time varied considerably [Figure 3] with a tendency for the percentage errors to increase [Figure 3]. The six patients with the highest changes in cardiac output, however, did not have the largest percentage errors in the readings of cardiac output between LiDCO and PulseCO, with the average error in this group being 17%.

This study assesses how well the PulseCO algorithm maintains its accuracy in a mixed group of critically ill patients. We deliberately chose to study critically ill patients whose cardiac output was being monitored for clinical reasons, as these are often the groups of patients that these devices are used in, but are rarely the groups of patients that they are validated for. Despite these challenging conditions we were able to demonstrate that the PulseCO algorithm is an acceptable method to measure cardiac output for up to four hours without re-calibration.

Continuous measurement of cardiac output is becoming increasingly popular. The two most popular devices that provide continuous CO from the analysis of arterial pressure waveform are the PiCCOplus (Pulsion medical system, Munich, Germany) [1, 4, 5]and Lidco™plus (LidCO, Cambridge, UK) [3, 7‐10]. PiCCOplus has been commercially available for longer and both its calibration system and continuous cardiac output system have been validated in different clinical scenes. The algorithm has been validated against both pulmonary and transpulmonary thermodilution. It has been demonstrated to be accurate so long as re-calibration is performed in case of major haemodynamic change[1, 2, 5]. Most of the validation studies of continuous cardiac output monitoring from the PiCCO system have been performed in patients undergoing either cardiac surgery or post operative patients on the Intensive Care Unit. Less is known about the accuracy of these continuous CO monitors in the critically ill population of patients.

LiDCO™plus, a more recently available system. has been validated against the pulmonary artery catheter and trans-pulmonary thermodilution in animals[3, 6, 11] and in different clinical scenarios in humans [7] including cardiac surgery and in post surgical patients [8‐10]. There are no data comparing subsequent readings from the PulseCO (after initial calibration) in a mixed adult intensive care population. Pitmann et al, compared PulseCO and LiDCO in post surgical patients[8]. Their data showed a good bias and limits of agreement at four and eight hours with an overall error of 27%. A previous study by Hamilton et al had also shown good agreement between PulseCO and LiDCO in patients following cardiac surgery [9]. In this study a similar protocol to ours was used, calibrating PulseCO at the beginning and then measuring PulseCO, LiDCO and intermittent thermodilution CO from the pulmonary artery catheter at baseline, 2, 4, 6 and 8 hours. Good agreements were found between the three methods. The authors concluded that following cardiac surgery PulseCO can be used without recalibration for at least eight hours.

This study has assessed the ability of the pulse power algorithm to maintain its accuracy when compared to the LiDCO against time. It has not compared the accuracy of the combination of LIDCO and PulseCO to give the absolute cardiac output. This would need a further independent measurement technique of cardiac output as a reference. In our population we found an acceptable agreement between PulseCO and LiDCO for the first four hours following calibration of the device and a reasonable ability of the algorithm to track changes in this variable within this time window. This agreement may in part relate to the wide range of cardiac outputs that our patients presented with in comparison to the relatively small changes in the variable seen over the first few hours. This raises the possibility that the relationship may in fact be a spurious artefact of the analysis rather than a real phenomenon. Four hours following calibration, however, the percentage error increased to levels that we had pre-defined as not being adequate. We calculated the percentage error of the limits of agreement as described by Critchley and Critchley[13]. This technique involves calculating the percentage error for agreement between two techniques. This is normally quoted as needing to be less than 30%. This does not mean that the error for the tested technique is 30%, as this is the value of the combination of both standard deviations. In deed if the reference technique has a precision of 10%, a value of 30% would roughly equate to a precision for the mew methodology of 10% also. At one, two and four hours the limits of agreement were 29%, 22% and 28% respectively. At eight hours the percentage error reached 36%. It must be stressed that the pulse pressure algorithm is essentially a software based computer equation, and therefore cannot cause increased errors over time. The increased errors can only be due to one of three causes- one degraded information from the arterial system, for instance from damping of the arterial signal, secondly due to a change in the individual patients haemodynamic profile, specifically changes in arterial compliance, resistance or impedance and lastly due to an error in the reference technique. We are confident in our patients that the arterial signal was of an optimal characteristic, as tested by the square wave test. The errors must therefore be due to either changing haemodynamic characteristics or a higher than expected variability in the lithium dilution cardiac output methodology.

Limitations of our study include the fact that we used a small number of patients in a single centre. Our population had a high level of heterogeneity therefore our results need to be confirmed by bigger studies with more homogeneous groups of patients. This may make our results less generalizable to other populations and settings. We chose to follow the manufacturer's recommendations for the measurement of cardiac output from the lithium dilution technique. This approach utilized only one lithium dilution curve. To our knowledge there is little data describing the inter and intra observer characteristics of performing this technique. To overcome this we ensured that only two researchers who were both extensively trained in the technique performed the measurements. It is of note, that Pittman in his study performed two calibration curves at each time point and in any case of more than 10% variability used an average of three measurements. We did not use this approach, and this may explain some of the variability. It is worth noting, however, that the technique we used is the method recommended by the manufacturers and is how this monitor is used in Intensive Care Units around the world regularly.

In conclusion we have found that in a mixed group of critically ill patients, the pulse power algorithm remained acceptable for the first four hours following calibration. This finding is valid for the whole group but may mask important changes on individual patients. We thus recommend in the critically ill patient group that the device should be re-calibrated at least every four hours. Until further data becomes available we would suggest re-calibration is performed utilizing at least two lithium dilution curves in order to reduce variability in the technique and improve accuracy. We would also suggest that for any patient where there is a significant change in the haemodynamic status it would be prudent to perform a re-calibration prior to initiating any major therapeutic change even if it is within this four hour window. Further studies should be performed to better understand exactly when re-calibrations should be performed for individual patients, as in some it may be significantly less than the fours hours suggested by this data.