Domestic cats respond to anesthesia in a manner that differs from that of other species, especially dogs. Cats are unique with regard to drug distribution and metabolism and cardiovascular depression caused by anesthetic agents, particularly inhalant anesthetics.1–3 Studies in which investigators used equipotent doses of halothane revealed that the CO of healthy cats decreased by > 50% in response to the inhalant anesthetic,3 whereas the change was < 20% in dogs and people.4 Cardiovascular depression is also evident clinically because severe hypotension is commonly encountered in healthy cats at surgical planes of anesthesia. In 2 studies5,6 in which investigators examined morbidity and fatalities in small animal practices, there was a higher mortality rate in cats than in dogs, especially when sick animals were compared. Heightened sensitivity of the feline cardiovascular system to anesthetic agents makes monitoring and management of that system an essential part of anesthetic procedures for cats. Close and detailed monitoring of cardiovascular variables allows early detection of changes in cardiovascular function and improves the ability of clinicians to effectively correct abnormalities. Cardiac output is arguably the most important variable in the evaluation of cardiovascular function because it most closely reflects systemic perfusion.
Several methods can be used for measuring CO. The most common is a thermodilution technique,7 and it is often considered the standard to which other techniques are compared. The thermodilution technique requires catheterization of the right side of the heart, which has inherent technical difficulties and risks.8,9 Moreover, there is some controversy in human medicine whether catheterization of the right side of the heart may be associated with an increase in fatalities.10 Another disadvantage of the thermodilution technique is that it only provides intermittent measurements, which precludes continuous monitoring of CO. For these reasons, the thermodilution technique and therefore determination of CO are rarely used in feline patients. This results in suboptimal monitoring of the cardiovascular system because measurement of blood pressure becomes the surrogate for measurement of blood flow. However, blood pressure is affected by both CO and vascular resistance, which limits its value in the assessment of cardiovascular function (particularly the flow component).
The TED technique was developed to allow noninvasive, easy-to-use, continuous monitoring of blood flow in the descending aorta.11 The transesophageal probe used in the study reported here consisted of 2 transducers. A pulsed-Doppler transducer estimates mean velocity of ABF, and an M-mode transducer measures the diameter of the aorta in the area in which flow velocity is measured.11–14 The device used this information to calculate blood flow in the descending aorta, which is used as an estimate of CO. Blood flow of the descending aorta constitutes approximately 70% of CO.15
The TED technique also has limitations. Velocity of blood flow is not uniform throughout a cross-sectional area of the aorta, the angle between the Doppler signal and direction of blood flow can only be estimated, and the cross-sectional area of the aorta can vary slightly during the cardiac cycle, all of which may add variability to results for the technique.16
Nevertheless, the TED method has been used in humans to estimate CO during anesthesia or in patients in critical care units, and it could be a good alternative to use of the thermodilution technique in cats. Studies to compare TED and thermodilution techniques for measurement of CO in humans have yielded results that have ranged from poor17 to strong11,15,18 correlations between the 2 methods.
The objective of the study reported here was to evaluate the TED technique for continuous estimation of CO in anesthetized cats. The study was designed to compare measurements obtained by use of the TED technique with those obtained by use of the thermodilution technique during normal, high, and low CO.
Materials and Methods
Animals—Six healthy conditioned domestic adult cats (mean ± SD body weight, 5 ± 0.7 kg) were used in the study. Cats were considered healthy on the basis of results of physical examination. The study protocol was approved by the Animal Use and Care Committee of the University of California, Davis, Calif.
Experimental design—Anesthesia was induced in a chamber by use of 5% isoflurane in oxygen. After induction of anesthesia, cats were orotracheally intubated, and anesthesia was maintained with 2% isoflurane (end-tidal concentration) in oxygen administered via a nonrebreathing circuit with a fresh gas flow of 500 mL/kg/min. Cats breathed spontaneously throughout the study. A catheter was percutaneously placed in a cephalic vein for the administration of lactated Ringer's solution at a rate of 3 mL/kg/h. A 5-F introducera was placed in the right jugular vein. A 4-F thermodilution catheterb was inserted via the introducer and positioned by use of fluoroscopic guidance such that the tip and thermistor were located in the pulmonary artery. A lead II ECGc was continuously monitored. Inspired and endtidal concentrations of isoflurane, oxygen, and carbon dioxide were continuously measured by use of a Raman spectrometer.d Hemoglobin oxygen saturation was continuously determined by use of pulse oximetry.e Systolic arterial pressure was measured before each CO measurement by use of a Doppler flow detector placed over a branch of the median artery and an occluding cuff attached to a sphygmomanometer. Core body temperature (measured at the level of the pulmonary artery by the thermistor of the thermodilution catheter) was maintained between 38° and 39°C by use of circulating warm water blankets and forced-air heat, as needed.
Cardiac output was determined, in triplicate, by use of a thermodilution technique and a CO computer.f Three milliliters of ice-cold 5% dextrose in water or saline (0.9% NaCl) solution was injected through the proximal port of the thermodilution catheter for each determination. Mean value of the 3 measurements was then calculated.
Aortic blood flow was continuously measured by use of a TED device.g A 7-mm probe was introduced into the esophagus through the oral cavity and positioned in the region where the descending aorta and esophagus are almost parallel. Fine adjustments of the probe position were then made by use of the M-mode until both aortic walls could be identified, and the widest aortic diameter was measured. Diameter of the descending aorta was then measured, flow velocity at that location was continuously determined, and ABF was calculated. Aortic blood flow was recorded concurrently with each CO determination.
After instrumentation was completed, 5 baseline measurements were concurrently obtained for CO and ABF at 5-minute intervals. Cats were then randomly assigned to a CO state (ie, high or low CO). High CO was achieved by decreasing the isoflurane concentration by 20% and administering a constant rate infusion of dobutamineh (5 to 20 μg/kg/min, IV), which was titrated to the rate needed to increase CO by at least 25% from the baseline value. Low CO was achieved by decreasing isoflurane concentration by 50% and administering medetomidinei (30 μg/kg, IV) to decrease CO by at least 25% from the baseline value. Isoflurane concentration was then adjusted to maintain a light plane of anesthesia. For each CO state, a stabilization period of 10 minutes was allowed and CO and ABF were measured concurrently (5 measurements obtained at 5-minute intervals). Baseline conditions were then restored by returning isoflurane to the previous concentration and discontinuing dobutamine infusion or administering the medetomidine antagonist atipamezolej (150 μg/kg, IV). After stabilization at baseline conditions for 10 minutes, concurrent CO and ABF measurements were again obtained. Cats were then assigned to the other CO state, which was induced by the aforementioned methods. Measurements were obtained as described previously. Baseline conditions were restored, and after stabilization for 10 minutes, a final set of CO and ABF measurements was obtained. At the end of the experiment, all catheters and monitoring equipment were removed, and the cats were closely observed until extubated and completely recovered from anesthesia.
Statistical analysis—Correlation between results for the 2 techniques was examined by use of the Pearson product-moment correlation for pooled data for all CO states and then separately for each CO state. Agreement was evaluated by use of the Bland-Altman method. Limits of agreement were defined as the mean difference between the 2 methods ± 1.96 SD of the differences. Gross deviation from the normality assumption was excluded on the basis of the elliptical pattern of a scatterplot of the data.19 To assess reproducibility of the TED measurements, the coefficient of variation of the measurement was calculated for each cat for each CO state and reported as mean ± SEM. All other data were reported as mean ± SD.
Results
A total of 150 data pairs of CO-ABF values were obtained for the 6 cats in the study. From these 150 data pairs, 90 were obtained at the baseline state, 30 were obtained at the high CO state, and 30 were obtained at the low CO state. Physiologic variables monitored during the various CO states were not statistically analyzed (Table 1). Total duration of anesthesia remained < 4 hours for all cats. Infusion rates of dobutamine required to achieve the targeted high CO state ranged from 5 to 7.5 μg/kg/min. The CO values obtained by use of the thermodilution technique ranged from 0.16 to 0.75 L/min, whereas the ABF values obtained by use of the TED technique ranged from 0.05 to 0.48 L/min (Table 2). By use of the measurements obtained at each CO state, ABF was 73 ± 14% of the CO determined at the baseline state by use of the thermodilution technique. During the high CO state, ABF was 61 ± 5% of CO, whereas during the low CO state, ABF was 54 ± 24%.
Mean ± SD values for physiologic variables during various CO states in 6 anesthetized cats.
| CO state* | SAP (mm Hg) | PETCO2 (mm Hg) | ETISO (%) | Spo2(%) | Temperature (°C)† |
|---|---|---|---|---|---|
| Baseline CO | 96 ± 13 | 41 ± 3 | 2.0 ± 0.2 | 99 ± 1 | 38.1 ± 0.4 |
| High CO | 123 ± 34 | 47 ± 3 | 1.9 ± 0.1 | 99 ± 1 | 38.4 ± 0.4 |
| Low CO | 161 ± 25 | 41 ± 6 | 1.0 ± 0.1 | 38.5 ± 0.6 |
Data were not statistically analyzed.
High CO was an increase of at least 25% from baseline CO, and low CO was a decrease of at least 25% from baseline CO.
Represents core body temperature.
SAP = Systolic arterial pressure. PETCO2 = End-tidal partial pressure of carbon dioxide, ETISO = End-tidal concentration of isoflurane. Spo2 = Hemoglobin saturation as measured by pulse oximetry. — = Unable to obtain a measurement.
Mean ± SD values for CO and ABF measured concurrently during various CO states in 6 anesthetized cats.
| CO state* | CO (L/min) | ABF (L/min) | ABF-to-CO ratio (%) |
|---|---|---|---|
| All CO states | 0.37 ± 0.15 | 0.25 ± 0.10 | 67 ± 17 |
| Baseline CO | 0.35 ± 0.07 | 0.25 ± 0.06 | 73 ± 14 |
| High CO | 0.61 ± 0.10 | 0.38 ± 0.07 | 61 ± 5 |
| Low CO | 0.20 ± 0.03 | 0.11 ± 0.05 | 54 ± 24 |
See Table 1 for key.
The ABF obtained by use of the TED technique had fairly low variability between measurements within each cat and each CO state. The coefficient of variation was 6.4 ± 1.0%.
Analysis of all data pairs collected during the study (n = 150) revealed a very good correlation between the thermodilution and TED techniques (r = 0.884; Figure 1; Table 3). Analysis of the data pairs on the basis of CO state (90 data pairs at baseline CO, 30 at high CO, and 30 at low CO) indicated that the correlation between techniques was very good at high CO (r = 0.886), less strong at baseline CO (r = 0.634), and weak at low CO (r = 0.413).
Correlation (95% confidence intervals) for CO (as determined by use of the thermodilution technique) and aortic blood flow (as determined by use of the TED technique) measured simultaneously at different states of CO in 6 anesthetized cats.
| CO state* | r* | Bias (L/min) | Limits of agreement (L/min) |
|---|---|---|---|
| Overall CO (n = 150) | 0.884 (0.84 to 0.91) | −0.125 | −0.277 to 0.028 |
| Baseline CO (n = 90) | 0.634 (0.49 to 0.74) | −0.099 | −0.210 to 0.012 |
| High CO (n = 30) | 0.886 (0.78 to 0.95) | −0.236 | −0.335 to −0.137 |
| Low CO (n = 30) | 0.413 (0.06 to 0.67) | −0.091 | −0.189 to 0.007 |
Bias represents the mean ditterence, and limits of agreement represent the bias ± 1.96 SD.
Representsthe Pearson product-moment correlation coefficient.
n = Number of pairs of measurements.
Linear regression and correlation between CO measured by use of a thermodilution technique (TDCO) and CO obtained by measurement of ABF by use of a TED technique (TEDCO) for baseline CO, high CO, and low CO (ie, all 150 data pairs) in 6 cats anesthetized with isoflurane. High CO was an increase of at least 25% from baseline CO, and low CO was a decrease of at least 25% from baseline CO. The line of best fit (solid line) and 95% confidence intervals (dotted lines) are indicated.
Citation: American Journal of Veterinary Research 69, 9; 10.2460/ajvr.69.9.1135
Linear regression and correlation between CO measured by use of a thermodilution technique (TDCO) and CO obtained by measurement of ABF by use of a TED technique (TEDCO) for baseline CO, high CO, and low CO (ie, all 150 data pairs) in 6 cats anesthetized with isoflurane. High CO was an increase of at least 25% from baseline CO, and low CO was a decrease of at least 25% from baseline CO. The line of best fit (solid line) and 95% confidence intervals (dotted lines) are indicated.
Citation: American Journal of Veterinary Research 69, 9; 10.2460/ajvr.69.9.1135
Linear regression and correlation between CO measured by use of a thermodilution technique (TDCO) and CO obtained by measurement of ABF by use of a TED technique (TEDCO) for baseline CO, high CO, and low CO (ie, all 150 data pairs) in 6 cats anesthetized with isoflurane. High CO was an increase of at least 25% from baseline CO, and low CO was a decrease of at least 25% from baseline CO. The line of best fit (solid line) and 95% confidence intervals (dotted lines) are indicated.
Citation: American Journal of Veterinary Research 69, 9; 10.2460/ajvr.69.9.1135
Bias and limits of agreement for all data pairs were −0.125 L/min and −0.277 to 0.028 L/min, respectively (Figure 2; Table 3). During high CO, the limits of agreement were −0.167 to −0.069 L/min, whereas the limits of agreement were 0.105 to 0.006 L/min at baseline CO and −0.094 to 0.003 L/min during low CO.
Bland-Altman plot of TDCO and TEDCO for baseline CO, high CO, and low CO (ie, all 150 data pairs) in 6 cats anesthetized with isoflurane. Bias (mean difference [dotted line]) and limits of agreement (bias ± 1.96 SD [dashed lines]) are indicated. See Figure 1 for remainder of key.
Citation: American Journal of Veterinary Research 69, 9; 10.2460/ajvr.69.9.1135
Bland-Altman plot of TDCO and TEDCO for baseline CO, high CO, and low CO (ie, all 150 data pairs) in 6 cats anesthetized with isoflurane. Bias (mean difference [dotted line]) and limits of agreement (bias ± 1.96 SD [dashed lines]) are indicated. See Figure 1 for remainder of key.
Citation: American Journal of Veterinary Research 69, 9; 10.2460/ajvr.69.9.1135
Bland-Altman plot of TDCO and TEDCO for baseline CO, high CO, and low CO (ie, all 150 data pairs) in 6 cats anesthetized with isoflurane. Bias (mean difference [dotted line]) and limits of agreement (bias ± 1.96 SD [dashed lines]) are indicated. See Figure 1 for remainder of key.
Citation: American Journal of Veterinary Research 69, 9; 10.2460/ajvr.69.9.1135
Discussion
Thermodilution is an extensively used and accepted method for determining CO to which other methods for measurement of CO are compared.7,20–22 In cats, thermodilution has been compared with almost all other known methods for measurement of CO,7,20,21,23 and it has provided minimal variability and good reproducibility. Thermodilution is considered a consistent and dependable method for measuring CO in cats7 and was selected for use in our study as the technique against which the TED technique would be compared. In addition, thermodilution allows repeated measurements to be performed safely, the indicator does not recirculate or accumulate, blood collections are not required, and results are not influenced by peripheral blood flow,21 all of which are aspects that make this technique appropriate to the study design.
The TED measurement of ABF had good correlation but weak agreement with CO measured by use of the thermodilution method in cats when the 150 data pairs were analyzed (ie, data for all CO states were included). This was expected because ABF is measured in the descending aorta and is therefore not equal to CO.15 Blood flowing to the brachiocephalic trunk is not measured by the TED technique, and this likely accounted for some of the differences between ABF and CO in the study reported here. Moreover, the proportion of CO reaching the descending aorta depends on the actual CO and is expected to be higher at a high CO than at a low CO because cardiac and cerebral blood flow are better preserved than the blood flow to other organs during low CO states.11,24,25
Overall analysis of the data pairs obtained in the study revealed a high correlation (r = 0.884) between results for the thermodilution and TED techniques. Comparison of the TED technique with the traditional thermodilution method for measuring CO in humans has revealed variable results that range from poor17 to strong11,15,18 correlations. The differences in results appear to be related, in part, to the type of device used. Older devices designed to measure ABF in humans calculated ABF on the basis of an estimated aortic diameter derived from a normogram that related a patient's height, weight, age, and gender,18 whereas the more recent ABF monitors, such as the one used in the study reported here, actually measure (by use of M-mode ultrasonography) the aortic diameter at the point where velocity of ABF is measured and therefore typically are more accurate.11,15
Analysis of the data pairs on the basis of CO state (ie, baseline CO, high CO, and low CO) revealed considerable variation for the correlation between the 2 techniques. Correlation was very good (r = 0.886) for high CO, less strong (r = 0.634) for baseline CO, and weak (r = 0.413) for low CO. Overestimation of CO by the thermodilution technique during low CO has been reported26 and could have been the cause of the weak correlation detected during the low CO state, although a decrease in the accuracy of the TED technique cannot be ruled out. It is also possible that the proportion of the CO reaching the descending aorta (where the measurement for the TED technique is obtained) is more variable at low CO than at high CO.
The agreement between techniques in our study was considered poor because the limits of agreement were −0.277 to 0.028 L/min for a mean CO of 0.37 L/min when all data pairs were analyzed and −0.210 to 0.012 L/min, −0.335 to −0.137 L/min, and −0.189 to 0.007 L/min for mean CO of 0.35 L/min, 0.61 L/min, and 0.20 L/min for data pairs obtained for baseline CO, high CO, and low CO, respectively. It has been suggested12 that changes in the diameter of the descending aorta induced by hemodynamic changes could be responsible for the variability of the limits of agreement reported in several studies.12,17,27–29 In addition, use of the TED technique reportedly underestimates changes in CO caused by changes in preload and contractility and overestimates changes caused by afterload and its influence on aortic diameter.30 In our study, even though dobutamine was used to increase CO and medetomidine was used to decrease CO, it is unlikely that the potential changes in aortic diameter caused by these drugs could explain the wide limits of agreement because aortic diameter was measured concurrently with measurement of ABF velocity.
Another aspect to be considered is that the absolute values of CO for a clinically normal adult domestic cat are much lower than those of an adult human, and a wide limit of agreement will be comparatively more clinically relevant in this situation. Therefore, ABF values obtained by use of the TED technique should be evaluated with caution because they do not correspond accurately to the absolute values of CO obtained by use of the thermodilution technique. In addition, it is important to consider that there is no criterion-referenced standard for measurement of CO because the real absolute CO cannot be measured and the thermodilution technique has some inherent variability.
Values for CO ranged from 0.16 to 0.75 L/min, whereas ABF values ranged from 0.05 to 0.48 L/min. Mean ± SD ABF-to-CO ratio during baseline conditions was 73 ± 14%, which is within the range of values determined in humans by use of similar methods.11,14,31 This ratio is likely to be influenced by physiologic and pathologic conditions that may alter the distribution of blood flow in the body. The contribution of ABF to the entire CO may change depending on the hemodynamic conditions. In the study reported here, the mean ABF-to-CO ratio was reduced from 73 ± 14% to 54 ± 24% during low CO, which could indicate a protective response of the body favoring blood flow to the head (brain) and heart. An increase in systemic vascular resistance attributable to adrenergic stimulation has been suggested as a physiologic mechanism.11 However, a problem related to the accuracy of the measurement technique during periods of hemodynamic instability cannot be discarded. Similar results have been reported11 whereby a decrease in the ABF-to-CO ratio was detected in patients with lower CO, and the lowest ratios were obtained with the lowest CO. On the other hand, a decrease in the ABF-to-CO ratio, even though less marked, was also detected for the high CO state in which the CO measured by use of the thermodilution technique increased more than did the ABF. An increase in the ABF-to-CO ratio has been detected after administration of a bolus of fluid11; however, when dobutamine was used to increase CO (similar to the technique used in the study reported here), changes in the ABF-to-CO ratio were not described.31
Values for the physiologic variables measured in the study reported here remained within expected limits throughout the various CO states. It is worth mentioning that during the low CO state, the pulse oximeter was unable to obtain a measurement in any of the cats. This was most likely a result of the intense peripheral vasoconstriction attributable to the use of α2-receptor agonist drugs, such as medetomidine. The increased systemic vascular resistance caused by medetomidine also explains the increase in systolic arterial pressure detected in the face of low CO.32,33
The TED technique provided good reproducibility, is relatively simple to use, and does not require specialized imaging skills. Adequate probe positioning was obtained in a timely and uneventful manner in all cats, and no incidents were noticed during use of the device. Although this method did not prove suitable to accurately measure absolute CO values, it can be used in the continuous assessment of patterns of CO and therefore could aid in prompt detection and correction of hemodynamic disturbances during anesthesia.
ABBREVIATIONS
| ABF | Aortic blood flow |
| CO | Cardiac output |
| TED | Transesophageal echo-Doppler ultrasonography |
Introducer kit, Arrow International, Reading, Pa.
Thermodilution balloon catheter, Arrow International, Reading, Pa.
Physiograph, Gould Instrument Systems, Valley View, Ohio.
Rascal II, Ohmeda, Salt Lake City.
N-20 PA, Nellcor, Pleasanton, Calif.
COM-1, American Edwards Laboratories, Irvine, Calif.
Hemosonic, Arrow International, Reading, Pa.
Dobutamine injection USP, Bedford Laboratories, Bedford, Ohio.
Domitor, Pfizer Animal Health, Exton, Pa.
Antisedan, Pfizer Animal Health, Exton, Pa
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