Cardiac output is a major determinant of oxygen delivery and is a dominant component of the hemodynamic profile, relevant for both research and clinical patient care. However, measuring cardiac output poses challenges due to limited equipment availability and the invasiveness and complex nature of the methods.
Direct measurement of cardiac output by an electromagnetic or ultrasound transit time flow probe (UTF) at the aortic root or main pulmonary artery is highly accurate and precise. However, the placement of the probe requires a thoracotomy, which limits the use of this method even in a research setting. Pulmonary arterial thermodilution (PATD) has been accepted as a clinical standard in people. However, this technique requires the placement of a pulmonary arterial catheter, which has been associated with higher morbidity in humans1 and can be challenging in small patients, such as cats. On the other hand, transpulmonary indicator dilution methods mitigate the risks associated with pulmonary arterial catheter placement. Several different indicators have been proposed such as temperature of blood, lithium, and ultrasound velocity of blood. Some of these have been evaluated against PATD in cats.2–4 Esophageal Doppler ultrasonography (EDU) converts descending aortic blood flow to cardiac output using a normogram in humans. It has demonstrated a good correlation with PATD for detecting changes in cardiac output.5 In cats, EDU had a poor agreement with PATD.6
The objectives of this study were to assess the agreement of transpulmonary thermodilution (TPTD) and transpulmonary ultrasound dilution (TPUD) against direct measurement of main pulmonary artery flow through UTF over a wide range of cardiac output in anesthetized cats. We also aimed to assess the trending ability of TPTD, TPUD, and EDU against UTF. We hypothesized that cardiac output measured by TPTD and TPUD was not interchangeable with UTF in anesthetized cats. We also hypothesized that all 3 techniques provide good trending ability.
Methods
Animals
This study was approved by the Auburn University IACUC. Twelve purpose-bred healthy adult cats were used. Eight cats were used in phase 1 including 1 used for pilot study and 4 used in phase 2 with 3 months apart between phases. Due to the invasiveness of the procedures, this was a nonsurvival study. Cats were scheduled for euthanasia from an unrelated project that complied with an approved IACUC protocol. Cats were provided care according to NIH guidelines and local laws and regulations. Cats were deemed healthy based on physical examination and no abnormal findings on a CBC and serum biochemistry panel.
Anesthetic protocol and instrumentation
Cats were sedated with IM alfaxalone (2 mg/kg) and midazolam (0.2 mg/kg). Then, a 20-gauge 1.5-inch IV catheter was placed in a cephalic vein, and anesthesia was induced with IV alfaxalone to effect. Cats were then orotracheally intubated, and anesthesia was maintained with isoflurane delivered in oxygen via a rebreathing anesthetic circuit and an out-of-circuit precision vaporizer and a continuous infusion of fentanyl at 3 to 10 µg/kg/h. All cats were mechanically ventilated throughout the experiment with a tidal volume of 10 mL/kg and a respiratory rate titrated to maintain an end-tidal carbon dioxide (ETco2) between 35 and 45 mmHg.
A 3-F thermistor-tipped thermodilution catheter (PiCCO; Getinge) was placed in a femoral artery through a cut-down procedure, and a 20-gauge, 12-cm single lumen central venous catheter was placed in a jugular vein. The correct location of the central venous catheter was confirmed by the presence of a central venous pressure waveform displayed on the monitor. Both the arterial catheter and the central venous catheter were connected to a brand-new, single-use, fluid-filled transducer with noncompliant tubing. The transducers were placed at the level of the manubrium and zeroed at atmospheric pressure. The arterial catheter transducer was connected to a pressurized bag containing heparinized saline to allow continuous flushing. Heart rate and rhythm, respiratory rate, rectal temperature, ETco2, end-tidal isoflurane concentration, direct arterial blood pressure, and central venous pressure were continuously monitored through a multiparameter monitor (MP70; Philips) that was serviced and calibrated before this study.
The UTF (8 and 10 mm; AU-series; Transonic) was surgically placed at the main pulmonary artery according to the manufacturer’s recommendations. The left lateral thoracic wall was aseptically prepared using a standard surgical scrub with chlorhexidine and alcohol, and a left thoracotomy was performed. After careful dissection, the probe liner and the flow probe were placed around the main pulmonary artery for cardiac output measurement. Coupling gel was generously applied between the probe and the pulmonary artery. A thoracostomy tube was placed before the closure of the thoracic wall and negative pressure was maintained by intermittent aspiration after closure. An indwelling urinary catheter was placed and connected to a closed system.
Measurement of cardiac output
Measurement of cardiac output at the main pulmonary artery was achieved by connecting the UTF to a console (TS 420; Transonic). The analog signal was converted to digital data through a data acquisition device (Powerlab 4/26; Powerlab) and continuously recorded by a laptop using commercially available software (LabChart; ADI instrument).
Transpulmonary thermodilution (PiCCO; Getinge) was performed according to the manufacturer’s recommendations using the module in the multiparameter monitor. A dose of 2 mL of ice-cold saline was injected through the central catheter over < 5 seconds at a steady rate, and the change in temperature was measured by the thermistor-tipped femoral catheter. Measurements were performed until 3 measurements with < 10% differences were obtained for each data point.
For the transpulmonary ultrasound dilution method (COStatus; Transonic), a dose of warm 0.9% saline (typically 3 mL) based on the calculations by the machine after manually entering cat demographic information was injected through the central catheter. Conversion of body surface area was based on a recent study.7 The reduction of ultrasonographic velocity due to blood dilution was detected by an ultrasound sensor located on the arterial side of a temporary extracorporeal circuit connecting the femoral arterial catheter and the central venous catheter. The flow rate of the extracorporeal circuit was set between 6 and 12 mL/min. After the measurement, the blood in the circuit was flushed back to the central vein to avoid blood loss from the measurements. Measurements were performed until 3 measurements with < 10% differences were obtained for each data point.
An esophageal Doppler transducer (ODMV+; Deltex Medical) was placed in the esophagus. The probe was placed to the level before the last rib and then gradually withdrawn and rotated in a stepwise fashion until the signal was lost. The probe was reinserted and adjusted to the location with the best signal. The probe was adjusted periodically to compensate for the movement from esophageal peristalsis. The descending aortic flow was measured with continuous wave Doppler. Optimal gain was adjusted to get the best image possible. The stroke distance and minute distance were calculated by the monitor. The cycles for calculation were set at a maximum setting of 20. In addition, post hoc analysis of the measurement was performed to average the measurement over a minute for each timepoint to mitigate the potential biases from single data.
During each measurement for all 3 devices, simultaneous recording of the measurement from the UTF was recorded. Post hoc verification from the stored data was also performed to ensure the accuracy of the data.
Electronic recording of waveform and biological data
The data from the multiparameter monitor and the EDU were continuously recorded using free access software (VitalRecorder). The hardware connection was set up via the recommendation of the software developer.8
Experiment protocol
After instrumentation, cats were subjected to the same order of treatments to create a wide range of cardiac output measurements (Figure 1): (1) baseline, (2) nontraumatic hemorrhage, (3) crystalloid fluid infusion, (4) autologous whole blood transfusion, (5) dobutamine infusion, (6) phenylephrine infusion, and (7) and high isoflurane concentration. Twenty minutes of stabilization were allowed after instrumentation and after each treatment before data collection for phases 1 to 4. In contrast, for phases 5 to 7, cardiac output measurements were performed immediately after each treatment, and a 20-minute washout period was allowed before proceeding to the following treatment. The order of measurements was EDU, TPTD, and then TPUD.
Experimental design and timeline. A total of 12 cats were used in this study. The star denotes when data were collected. DB = Dobutamine infusion (10 μg/kg/min). FB = Balanced crystalloid solution (20 mL/kg; pHyLyte; Dechra) over 20 minutes. HR = Atraumatic hemorrhage (20 mL/kg) over 20 minutes. IS = High-isoflurane concentration. IVC = IV catheterization. PH = Phenylephrine infusion (3 μg/kg/min). S = Stabilization period. TR = Autotransfusion of 20 mL/kg heparinized whole blood.
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.24.09.0263
Nontraumatic hemorrhage was performed by removing 20 mL/kg of whole blood over 20 minutes through the jugular catheter by hand. The retrieved whole blood was stored in sterile heparinized syringes at a ratio of 10 units of heparin to 1 mL of whole blood. The whole blood was placed in a cooler on ice until autologous transfusion. The crystalloid infusion was performed by administering a total of 20 mL/kg of a balanced crystalloid solution (pHyLyte; Dechra) over 20 minutes. Autologous transfusion was administered through an inline filter (Hemo-Nate Utah Medical) over 20 minutes. Dobutamine was infused at 10 µg/kg/min, and phenylephrine was infused at 3 µg/kg/min for a total of 20 minutes before data collection. Finally, the vaporizer was adjusted to achieve an end-tidal isoflurane concentration of 2% for 20 minutes. After the first 4 cases, end-tidal isoflurane was adjusted to achieve either mean arterial pressure of 40 mmHg or cardiac output < 0.1 L/min for 20 minutes before data collection. At the end of the data collection, anesthetized cats were humanely euthanized with an IV injection of a pentobarbital-based euthanasia solution.
Statistical analysis
A convenient sample size based on the availability of the animals was used. All analysis was performed using MedCalc (22.016) and the RStudio IDE, version 2023.06.0 + 421 (RStudio Team, 2022), and R, version 4.4.0 (2024-04-24; R Core Team, 2022).9
Assessment of calibration
The Spearman rank correlation coefficient was used to evaluate the correlation between TPTD and TPUD to UTF. Data were fitted with a linear mixed effect model to derive a calibration equation using an independent variable of TPTD and TPUD and a dependent variable of UTF considering UTF as the gold standard method. The likelihood ratio test between models with and without cat as a random intercept and with and without random slope was used to determine if and how random effect is included in the final model. Repeated k-fold cross-validation was implemented to assess the calibration equation, with k set at 10 and 100 repetitions performed. The same comparison was also performed on the percentage changes using the average of measurements in each phase. In other words, this is to assess the calibration equation for the 4-quadrant plot used for trending analysis.
Assessment of agreement
The normality of the differences was assessed by the Shapiro-Wilk test and visual inspection of the histogram and the Q-Q plot.
The precision of the UTF is 2% according to the manufacturer.
Assessment of trending
Trending ability of TPTD, TPUD, and EDU was assessed with a 4-quadrant plot using percentage change.12 Both cardiac output against minute distance and stroke volume against stroke distance were analyzed for EDU, but only cardiac output against cardiac output was analyzed for TPTD and TPUD. The average of measurements in each phase was used, and the percentage change was calculated by dividing the difference by the reading before changes. The concordance rate is calculated by determining the percentage of observations that fall within the first and third quadrants. A concordance rate > 95% was deemed acceptable. When both observations fell within a 12% range, they were excluded from the concordance rate calculation. The exclusion zone was selected considering the 95% CI of least significant change of TPTD and TPUD as well as conventional fluid responsiveness aiming for 10% to 15% cardiac output changes.
Assessment of precision
The coefficient of variation of the repeated measurements in each phase for TPTD and TPUD was calculated by the SD divided by the mean. The coefficient of error was calculated by dividing the coefficient of variation by the square root of the number of measurements. The least significant change was calculated by 2.77 times the coefficient of error.13,14 The average and 95% CI of the coefficient of variation and least significant change were reported.
Results
Data from the cat used in the pilot study were not included in the analysis. The initial study design was to place the cats in dorsal recumbency, but both TPTD and TPUD failed to generate readings during the pilot study. After the cat was euthanized, it was found that the thermistor-tipped thermodilution catheter had become kinked due to the change in position. Consequently, the subsequent cats were placed in sternal recumbency following lateral thoracotomy to prevent a repeat of this complication. The range of measurements from UTF was 0.1 to 0.94 L/min.
Esophageal Doppler
Two out of 11 cats were not included in the trending analysis for EDU. These 2 cats experienced a ruptured pulmonary artery due to surgical complications. One cat was deemed unrepairable and was euthanized immediately without further data collection. The other cat was repairable, so data collection continued for an unrelated study, although no UTF probe was placed. The remaining 9 cats were aged 5.7 ± 2.75 years old with a mean weight of 3.56 kg (2.8 to 3.98 kg). A total of 54 data points were eligible for the trending analysis, as changes occurred only after the baseline. Five dobutamine waveforms and 1 phenylephrine waveform were too high to read. Therefore, only 42 data sets were used since missing data from 1 phase would cause the loss of 2 changes. Two and 3 data sets for each of stroke volume versus stroke distance and cardiac output versus minute distance were excluded from the concordance rate calculation due to both readings having < 12% changes. The concordance rate for cardiac output versus minute distance was 64%, and stroke volume versus stroke distance was 65% (Figure 2).
Trending analysis of esophageal Doppler ultrasonography using 4-quadrant plot with each dot representing a paired measurement. The x-axis is percentage changes of stroke volume (A) and cardiac output (B) measured by perivascular ultrasound transit time flow probe (URF) around main pulmonary artery. The y-axis is percentage change of stroke distance (A) and minute distance (B) measured by esophageal Doppler ultrasonography. No data were excluded in this plot. A total of 9 anesthetized cats were used.
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.24.09.0263
Transpulmonary indicator dilution methods
Three out of 11 cats were not included in the analysis for TPTD and TPUD. Two out of the 3 cats were the same 2 cats described above. The third cat suffered equipment malfunction: both TPTD and TPUD failed to generate any readings. However, data from EDU and the unrelated study were collected in this cat. The remaining 8 cats aged 5.8 ± 2.9 years old and with a mean weight of 3.5 kg (2.8 to 3.98 kg).
Transpulmonary thermodilution
Transpulmonary thermodilution failed to obtain readings after hemorrhage in 1 cat, and the signal quality of UTF decreased to an unacceptable level after hemorrhage in another cat. However, it returned to an acceptable range after fluid bolus. Consequently, a total of 54 data points were available for Bland-Altman analysis, while 44 data points were available for trending analysis.
For calibration, the Spearman rank correlation coefficient of TPTD versus UTF was 0.89 (95% CI 0.82 to 0.94). The best model for fit of data included use of a random intercept and a random slope. The significant coefficient was 0.94 with an SE of 0.07, and significant intercept was −0.048 with SE of 0.024. Repeated k-fold cross-validation showed mean absolute error and root mean squared error of 0.043 and 0.059 L·min−1, respectively.
The difference between TPTD and UTF was normally distributed. For Bland-Altman analysis (Figure 3), the bias was −0.084 L·min−1. The upper limit of the level of agreement was 0.092 (95% CI, 0.026 to 0.24) L·min−1, and the lower limit of the level of agreement was −0.26 (95% CI, −0.41 to −0.19) L·min−1. The percentage error was 38.2%. The simplified total error was 5.9%.
Bland-Altman with repeated measures plot between transpulmonary thermodilution and perivascular UTF. The 95% CI of upper and lower limit of level of agreement is plotted in addition to the bias. The x-axis is the average, and the y-axis is the difference between UTF and transpulmonary thermodilution (TPTD). A total of 8 anesthetized cats were used. Paired measurements from the same cats are presented with the same mark.
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.24.09.0263
Eight data points were excluded from trending analysis due to both readings changing < 12%. The concordance rate for TPTD was 100% (Figure 4). The random effect did not significantly improve the model of percentage changes between TPTD and UTF so simple linear regression was used and showed an adjusted R2 of 0.93, significant coefficient of 1.23 with SE of 0.058, and nonsignificant intercept of 4.32 with SE of 2.19. Repeated k-fold cross-validation showed an R2, mean absolute error, and root mean squared error of 0.95%, 9.2%, and 11.8%, respectively.
Trending analysis using 4-quadrant plot between UTF and TPTD (A) and transpulmonary ultrasound dilution (TPUD; B). The x-axis is percentage changes of UTF, and y-axis is percentage change of TPTD (A) and TPUD (B). No data were excluded in this plot.
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.24.09.0263
Transpulmonary ultrasound dilution
The cat with unacceptable signal quality after hemorrhage during TPTD regained acceptable signal during measurements for TPUD. Therefore for TPUD, a total of 56 data points were available for Bland-Altman analysis, and a total of 48 data points were available for trending analysis.
For calibration, the Spearman rank correlation coefficient of TPUD versus UTF was 0.80 (0.67 to 0.88). The best model included random intercept and random slope. The significant coefficient was 0.78 with an SE of 0.10, and the nonsignificant intercept was 0.059 with an SE of 0.027. Repeated k-fold cross-validation showed mean absolute error and root mean squared error of 0.042 and 0.055 L·min−1, respectively.
The difference between TPUD and UTF was normally distributed. For Bland-Altman analysis (Figure 5), the bias was −0.041 L·min−1. The upper limit of the level of agreement was 0.19 (95% CI, 0.11 to 0.38) L·min−1, and the lower limit of the level of agreement was −0.28 (95% CI, −0.47 to −0.19) L·min−1. The percentage error was 52.9%. The simplified total error was 5.8%.
Bland-Altman with repeated measures plot between transpulmonary ultrasound dilution and perivascular UTF. The 95% CI of upper and lower limit of level of agreement is plotted in addition to the bias. The x-axis is the average, and the y-axis is the difference between UTF and TPUD. A total of 8 anesthetized cats were used. Paired measurements from the same cats are presented with the same mark.
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.24.09.0263
Three data points were excluded from trending analysis due to both readings changing < 12%. The concordance rate for TPUD was 95.5% (Figure 4). The random effect did not significantly improve the model of percentage changes between TPUD and UTF, so simple linear regression was used and showed an adjusted R2 of 0.82, significant coefficient of 0.80 with SE of 0.056, and nonsignificant intercept of 0.76 with SE of 2.82. Repeated k-fold cross-validation showed an R2, mean absolute error, and root mean squared error of 0.89%, 14.6%, and 18.0%, respectively.
Precision
The average and 95% CI of the coefficient of variation of TPTD and TPUD were 5.6% (3.6% to 7.4%) and 5.4% (4.3% to 6.4%), respectively. The average and 95% CI of the least significant change of TPTD and TPUD were 8.7% (5.6% to 11.8%) and 8.6% (6.9% to 10.2%), respectively.
Discussion
Three cardiac output measurement methods were compared to the gold standard: perivascular UTF in anesthetized cats in this study. The results showed both TPTD and TPUD had low bias. However, both methods had a wide level of agreement in the Bland-Altman plot and therefore are not considered to be interchangeable with UTF. Additionally, both TPTD and TPUD showed imprecise trending despite an acceptable ability to detect the direction of changes. On the contrary, EDU showed poor trending ability.
A commonly used reference method in the literature for cardiac output measurement technique evaluation is PATD. The PATD method has the advantages of (1) being easy to use, (2) being commonly used in clinical practice, (3) allowing measurement of a multitude of additional hemodynamic parameters with modern pulmonary arterial catheters, (4) allowing for repeat measurements, and (5) requiring minimal blood sampling. However, the safety, accuracy, and precision of PATD have been challenged1,15–21 and eventually led to a wave of innovation and research on alternative technologies for cardiac output measurement. However, it is prudent to point out that it would be ideal to evaluate cardiac output measurement methods against a true gold standard such as a perivascular flow probe whenever possible instead of a clinical standard such as PATD since the clinical standard could be challenged and become obsolete. The utilization of ultrasound transit time to measure flow was developed by Drost in 1978.22 The modern perivascular flow probe utilizes X-pattern ultrasound transit time transducers to measure blood flow in the vessels. It has been validated23,24 and has been widely used clinically and in research. The coupling between the UTF and the vessel relies on coupling gel. As a result, the UTF can fit around the vessel loosely, allowing for lateral wall excursions from pulsatile flow. In contrast, the electromagnetic flow probe has been shown to affect right ventricular afterload when placed on the main pulmonary artery.25 By using the UTF, this study provided a more definitive evaluation of the 3 cardiac output measurement techniques in anesthetized cats.
Bland-Altman analysis is the most popular method to assess agreement between 2 methods.26 It provides insights for useful information such as bias and level of agreement. Several recent reviews27–30 have recommendations and checklists to ensure standardized reporting and good-quality analysis. Percentage error has been historically used to assess interchangeability and to compare Bland-Altman analysis results across the study. Essentially, percentage error is the level of agreement calibrated by the mean of the measurements. A cutoff of 30% has been proposed and commonly cited.11 However, the rationale of the 30% cutoff was not always recognized and resulted in the cutoff being misused frequently. It was clearly explained in the original study that the total error was simplified and assumed to be the square root of the sum of square precision of each method (
On the other hand, the 4-quadrant plot showed a concordance rate of 100% and 95.5% for TPTD and TPUD, respectively. Therefore, one may argue that both of these devices are clinically useful since there is not a widely agreed upon normal cardiac output range and it is the changes that clinicians are interested in. However, it is important to point out that, despite commonly being used, the concordance rate calculation for the 4-quadrant plot is a very crude and qualitative assessment of the trending ability. For example, the concordance rate does not show how dispersed the data points are around the identity line of the 4-quadrant plot.
Because the UTF is a precise method and deemed the gold standard, this study also evaluated if one can use a calibration equation to convert readings from TPTD and TPUD to UTF and how well the calibration equation performed for both of the raw data and the percentage changes of the average data in each phase. The mean absolute error from repeated k-fold cross-validation of TPTD and TPUD raw data was 0.043 and 0.042 L·min−1, respectively. This may not seem to be very significant; however, it is around 12% of the average of baseline cardiac output (0.35 L·min−1). Similar results were seen for the percentage change of the average measurements in each phase where the mean absolute error was 9.2% and 14.6% for TPTD and TPUD, respectively. Therefore, either clinical or research use of TPTD and TPUD warrants careful consideration of these limitations.
Transpulmonary indicator dilution has some practical and theoretical advantages over PATD. First, transpulmonary indicator dilution does not require pulmonary arterial catheterization, which has been shown to carry more risks than benefits in humans.1 Second, transpulmonary indicator dilution provides several hemodynamic parameters on top of the cardiac output measurement. In addition, PATD measures right ventricular output, which may be affected by respiratory variation31 and the transient bradycardia induced by the cold saline injection. Therefore, the inherently longer measurement time of TPTD may ameliorate the above limitations and provide better readings. However, indicator loss and recirculation due to traveling through the right heart, lung, left heart, and segment of the aorta and the longer measurement time may also compromise the readings of transpulmonary indicator dilution.32,33 However, 1 study34 showed there was insignificant indicator loss in TPTD.
Similar to this study, TPTD showed low bias when compared to the Fick method in children and infants35,36 and when compared to UTF in lambs.37 Nevertheless, the aforementioned studies35,36,37 showed a lower percentage error (approx 10% to 20%) compared to this study. However, the study37 in lambs only investigated baseline, hypovolemia, and volume loading conditions, and the study35,36 in children and infants was performed in stable patients in contrast to this study, which exposed the subjects to several different conditions and may partially explain the differences in the percentage error. Additionally, the subjects were larger, and the range of cardiac output was higher in the above studies compared to this study in cats. It is possible that the size of the subjects and the range of cardiac output had influences on the percentage error. Indeed, it was pointed out by de Boode et al38 that percentage error would increase in the lower cardiac output range if the standard deviation of the bias remained constant disregarding the cardiac output. Since the average cardiac output is the denominator, the lower the cardiac output the higher the percentage error.
On the other hand, TPUD has been more extensively evaluated in vitro and in vivo against UTF in animals and humans.38–45 There were 2 in vivo studies38,40 done in piglets. One compared 2 different injectate volume38 and the other compared 2 different injectate temperatures.40 There were no significant differences between 0.5 and 1 mL/kg injectate,38 but the body temperature injectate performed better than the room temperature injectate.40 Similar to TPTD, both studies38,40 showed low bias and good trending abilities consistent with this study but low percentage error (approx 22% to 27%) in contrast to this study. On the other hand, similar findings were shown in human pediatric patients when TPUD was compared to UTF,39,43 but a higher percentage error was found when TPUD was compared to the Fick method.44,45 Similar to TPTD, these studies used larger subjects and evaluated a higher range of cardiac output.
The EDU did not provide acceptable trending ability in this study. This is consistent with the results from a study46 in pigs when compared to the Fick method under hemorrhagic shock, a study47 in pigs when compared to UTF under various conditions, and a study48 in dogs when compared to UTF under various conditions. One potential explanation is that the assumption of fixed ascending to descending aortic flow is invalid. Extensive literature49–51 demonstrates that regional organ blood flow is altered by shock and various vasoactive agents. Additionally, the aorta is an elastic organ in which the area is pressure dependent52 and influenced by vasoactive agents.53 It has been shown that taking the cross-sectional area into account improves the performance of EDU and should be considered in future studies.54,55
There are some limitations and strengths to this study. First, the sample size was a convenience sample and relatively small, which was reflected on the wide 95% CI of the upper and lower limits of the limits of agreement. Several methods have been proposed to determine the sample size for the agreement study.56 Nonetheless, sample size calculation for the study design with repeated measurements within subjects such as this study still presents an unsolved issue. Additionally, this study was performed in 2 phases due to the challenges faced in instrumentation. Confounding factors cannot be totally ruled out despite the same protocol being followed. Transthoracic echocardiography was not performed, so occult cardiac disease cannot be ruled out. Therefore, cardiac diseases such as hypertrophic cardiomyopathy, left ventricular outflow tract obstruction, and accompanied mitral regurgitation may induce biases if present. Finally, TPTD, TPUD, and EDU all allow measurements of several additional hemodynamic parameters that were not evaluated in this study and may provide clinically useful information that warrants future study. On the other hand, direct measurements of cardiac output were performed, and a wide range of hemodynamic conditions mimicking clinical scenarios and a wide range of changes were applied. These allow a thorough evaluation of the technologies.
In conclusion, both TPTD and TPUD did not provide satisfactory performance for measuring cardiac output in anesthetized cats. However, both technologies may provide reasonable trending ability after considering the limitations of precision. On the other hand, utilization of the stroke distance and minute distance from EDU requires further evaluation after incorporating the pressure-dependent aortic cross-sectional area.
Acknowledgments
The authors thank Scott-Ritchey Research Center, Jessica Cannon, and Taylor Moss for collaboration and technical support.
Disclosures
The authors have nothing to disclose.
ChatGPT was used for the revision of this manuscript.
Funding
This study was funded by start-up funds from the Department of Clinical Sciences of Auburn University.
ORCID
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