• View in gallery

    Plots of within-subject SD versus the subject mean for CI measured by use of LiDCO (A) or NICO (B) methods in 18 foals in 2 studies.4,5 A subject was defined as a specific foal for a particular physiologic state. Notice the 1 extreme outlier for NICO, which was considered to be a valid observation.

  • View in gallery

    Bland-Altman plot of subject bias and precision (ie, limits of agreement; 1.96 X SD) determined by use of replicated measurements for 18 foals in 2 studies.4,5 The solid horizontal line indicates the mean bias of the measurements, the dotted horizontal lines depict the limits of agreement, and the dashed lines around each dotted line represent the 95% confidence intervals of the limits of agreement. See Figure 1 for remainder of key.

  • View in gallery

    Linear regression for a wide range of CI values measured concurrently by LiDCO and NICO methods in 18 anesthetized foals in 2 studies.4,5 The solid line indicates the best fit, and dashed lines indicate 95% confidence intervals. There was good correlation (r = 0.77) between the methods. Equation for the slope of the line was as follows: y = 4.37 + 0.87x, which indicates that LiDCO = 4.37 + [0.87 X NICO]).

  • 1

    Thomas WP, Madigan JE, Backus KQ, et al. Systemic and pulmonary haemodynamics in normal neonatal foals. J Reprod Fertil Suppl 1987;35:623628.

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    Lavoie JP, Madigan JE, Cullor JS, et al. Haemodynamic, pathological, haematological and behavioural changes during endotoxin infusion in equine neonates. Equine Vet J 1990;22:2329.

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    Corley KTT, Donaldson LL, Furr MO. Comparison of lithium dilution and thermodilution cardiac output measurements in anaesthetised neonatal foals. Equine Vet J 2002;34:598601.

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    Giguère S, Bucki E, Adin DB, et al. Cardiac output measurement by carbon dioxide rebreathing, 2-dimensional echocardiography, and lithium-dilution method in anesthetized neonatal foals. J Vet Intern Med 2005;19:737743.

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    Valverde A, Giguère S, Sanchez LC, et al. Effects of dobutamine, norepinephrine, and vasopressin on cardiovascular function in anesthetized neonatal foals with induced hypotension. Am J Vet Res 2006;67:17301737.

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    Linton RA, Young LE, Marlin DJ, et al. Cardiac output measured by lithium dilution, thermodilution, and transesophageal Doppler echocardiography in anesthetized horses. Am J Vet Res 2000;61:731737.

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    Kurita T, Morita K, Kato S, et al. Comparison of the accuracy of the lithium dilution technique with the thermodilution technique for measurement of cardiac output. Br J Anaesth 1997;70:770775.

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    Botte A, Leclerc F, Riou Y, et al. Evaluation of a noninvasive cardiac output monitor in mechanically ventilated children. Pediatr Crit Care Med 2006;7:231236.

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    Mason DJ, O’Grady M, Woods JP, et al. Effect of background serum lithium concentrations on the accuracy of lithium dilution cardiac output determination in dogs. Am J Vet Res 2002;63:10481052.

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    Gama de Abreu M, Winkler T, Pahlitzsch T, et al. Performance of the partial CO2 rebreathing technique under different hemodynamic and ventilation/perfusion matching conditions. Crit Care Med 2003;31:543551.

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    Gunkel CI, Valverde A, Morey TE, et al. Comparison of non-invasive cardiac output measurement by partial carbon dioxide rebreathing with the lithium dilution method in anesthetized dogs. J Vet Emerg Crit Care 2004;14:187195.

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    Odenstedt H, Stenqvist O, Lundin S. Clinical evaluation of a partial CO2 rebreathing technique for cardiac output monitoring in critically ill patients. Acta Anaesthesiol Scand 2002;46:152159.

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    Tachibana K, Imanaka H, Takeuchi M, et al. Noninvasive cardiac output measurement using partial carbon dioxide rebreathing is less accurate at settings of reduced minute ventilation and when spontaneous breathing is present. Anesthesiology 2003;98:830837.

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Comparison of noninvasive cardiac output measured by use of partial carbon dioxide rebreathing or the lithium dilution method in anesthetized foals

Alexander Valverde DVM, DVSc1, Steeve Giguère VMD, PhD2, Timothy E. Morey MD3, L. Chris Sanchez DVM, PhD4, and Andre Shih DVM5
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  • 1 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
  • | 2 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
  • | 3 Department of Anesthesiology, College of Medicine, University of Florida, Gainesville, FL 32610.
  • | 4 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
  • | 5 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

Abstract

Objective—To compare cardiac output (CO) measured by use of the partial carbon dioxide rebreathing method (NICO) or lithium dilution method (LiDCO) in anesthetized foals.

Sample Population—Data reported in 2 other studies for 18 neonatal foals that weighed 32 to 61 kg.

Procedures—Foals were anesthetized and instrumented to measure direct blood pressure, heart rate, arterial blood gases, end-tidal isoflurane and carbon dioxide concentrations, and CO. Various COs were achieved by administration of dobutamine, norepinephrine, vasopressin, phenylephrine, and isoflurane to allow comparisons between LiDCO and NICO methods. Measurements were obtained in duplicate or triplicate. We allowed 2 minutes between measurements for LiDCO and 3 minutes for NICO after achieving a stable hemodynamic plane for at least 10 to 15 minutes at each CO.

Results—217 comparisons were made. Correlation (r = 0.77) was good between the 2 methods for all determinations. Mean ± SD measurements of cardiac index for all comparisons with the LiDCO and NICO methods were 138 ± 62 mL/kg/min (range, 40 to 381 mL/kg/min) and 154 ± 55 mL/kg/min (range, 54 to 358 mL/kg/min), respectively. Mean difference (bias) between LiDCO and NICO measurements was −17.3 mL/kg/min with a precision (1.96 × SD) of 114 mL/kg/min (range, −131.3 to 96.7). Mean of the differences of LiDCO and NICO measurements was 4.37 + (0.87 × NICO value).

Conclusions and Clinical Relevance—The NICO method is a viable, noninvasive method for determination of CO in neonatal foals with normal respiratory function. It compares well with the more invasive LiDCO method.

Abstract

Objective—To compare cardiac output (CO) measured by use of the partial carbon dioxide rebreathing method (NICO) or lithium dilution method (LiDCO) in anesthetized foals.

Sample Population—Data reported in 2 other studies for 18 neonatal foals that weighed 32 to 61 kg.

Procedures—Foals were anesthetized and instrumented to measure direct blood pressure, heart rate, arterial blood gases, end-tidal isoflurane and carbon dioxide concentrations, and CO. Various COs were achieved by administration of dobutamine, norepinephrine, vasopressin, phenylephrine, and isoflurane to allow comparisons between LiDCO and NICO methods. Measurements were obtained in duplicate or triplicate. We allowed 2 minutes between measurements for LiDCO and 3 minutes for NICO after achieving a stable hemodynamic plane for at least 10 to 15 minutes at each CO.

Results—217 comparisons were made. Correlation (r = 0.77) was good between the 2 methods for all determinations. Mean ± SD measurements of cardiac index for all comparisons with the LiDCO and NICO methods were 138 ± 62 mL/kg/min (range, 40 to 381 mL/kg/min) and 154 ± 55 mL/kg/min (range, 54 to 358 mL/kg/min), respectively. Mean difference (bias) between LiDCO and NICO measurements was −17.3 mL/kg/min with a precision (1.96 × SD) of 114 mL/kg/min (range, −131.3 to 96.7). Mean of the differences of LiDCO and NICO measurements was 4.37 + (0.87 × NICO value).

Conclusions and Clinical Relevance—The NICO method is a viable, noninvasive method for determination of CO in neonatal foals with normal respiratory function. It compares well with the more invasive LiDCO method.

Cardiovascular monitoring in anesthetized neonatal foals often does not include CO determinations because of the invasiveness of most methods. Thermodilution and LiDCO are accepted methods for CO determination in foals. However, most studies1–4 in which investigators evaluated these techniques have been conducted in controlled research conditions1–4 because of the required invasive instrumentation of the patients, which includes catheterization of the right side of the heart and pulmonary artery for thermodilution and catheterization of a peripheral artery for LiDCO. Thus, use of thermodilution or LiDCO is typically not considered practical in a clinical setting.

Other less invasive methods, including transthoracic echocardiography and NICO, have been evaluated in anesthetized neonatal foals as alternatives to LiDCO.4 In that study, volumetric echocardiography by use of the Bullet method provided the best correlation to a wide range of CO values induced by various degrees of anesthetic depth in combination with inotropic or vasopressor support. Comparisons between the LiDCO and NICO methods included mean values for duplicate or triplicate LiDCO measurements, with a single NICO value obtained during the period required to complete the LiDCO determinations.

Because echocardiography may also be impractical in anesthetized patients undergoing surgery, for the study reported here, we collated data from 1 study4 with additional data obtained by the same laboratory group5 to establish the usefulness of the NICO method. The objective of the study reported here was to compare the NICO and LiDCO methods by use of single measurements obtained by use of both methods in anesthetized foals in which a full range of CO and arterial blood pressure values was manipulated by anesthetic depth and use of inotropic or vasopressor drugs, including dobutamine, norepinephrine, vasopressin, and phenylephrine.

Materials and Methods

Sample population—Data obtained for 18 neonatal foals (9 males and 9 females) between 1 and 6 days old and weighing 32 to 61 kg were published in 2 studies.4,5 Those data were collated and used in the study reported here. Birth of all foals was uneventful at the end of a full-term gestation. Foals were considered healthy on the basis of results of a complete physical examination and assessment of adequate transfer of passive immunity, which was confirmed by measurement of plasma IgG concentration by use of a commercial immunoassay.a The 2 studies4,5 were approved by the Institutional Animal Care and Use Committee of the University of Florida.

Anesthesia and instrumentation—Several procedures were performed during completion of the 2 studies.4,5 The anesthetic procedure performed during completion of the 2 studies included insertion of a 16-gauge, 2- or 12-inch catheter in the right jugular vein for subsequent induction of general anesthesia. In the first study,4 10 foals were sedated by IV injection of xylazine hydrochlorideb (1.0 mg/kg), whereas in the second study,5 8 foals were sedated by IV injection of diazepamc (0.05 mg/kg). In both studies, anesthesia was induced by IV injection of ketamine hydrochlorided (2.0 mg/kg).

For both studies,4,5 foals were positioned in left lateral recumbency. An orotracheal tube was inserted for maintenance of anesthesia by administration of isofluranee in oxygen by use of a rebreathing circuit system. Oxygen flow rate was 2 to 3 L/min, and end-tidal isoflurane concentration was monitored by use of an infrared gas analyzerf calibrated before each experiment with a standardized calibration gas mixtureg designed for the analyzer.

Foals were mechanically ventilated at a rate of 8 to 10 breaths/min and a tidal volume of 10 to 15 mL/kg to maintain the ETCO2 concentration between 40 and 50 mm Hg. Because the primary objectives differed between the 2 studies, ETCO2 concentrations differed for foals in each study. In foals of the first study,4 the ETCO2 concentration was maintained constant within the desired range. However, the second study,5 the ETCO2 concentration was maintained constant for only the first 30 minutes of anesthesia; subsequently, the respiratory rate was kept constant but with no attempt to correct the ETCO2 concentration thereafter.

A 20-gauge, 1.88-inch catheter was inserted in the right metatarsal artery for measurements of direct blood pressure and CO. An electronic pressure transducerf was positioned and calibrated to 0 at the level of the sternal manubrium for continuous monitoring of SAP, DAP, and MAP. Heart rate and ECG were also monitored throughout the experiments. Normovolemia and normoglycemia were maintained throughout the experiments by administration of a balanced electrolyte solutionh (5 mL/kg/h, IV). Body temperature was monitored electronically and maintained between 37.5° and 39°C by use of a blanket.

Measurement of CO by LiDCO—A lithium dilution cardiac computeri was used to determine CO during both studies.4,5 The hemoglobin concentration and serum sodium concentration required for this method were measured by use of a blood gas analyzerj immediately before CO determination. The sensork for measurement of lithium chloride in blood was placed between the side port of a 3-way valve and connected to the catheter inserted in the metatarsal artery. Extension tubing that passed through a peristaltic pump directed blood to a collection bag at a flow rate of 4 mL/min across the sensor. The dose of lithium chloridel (0.16 to 0.28 mmol) was placed in an extension set attached to the catheter inserted in the jugular vein; the dose was administered, and the extension set was flushed with 8 to 12 mL of heparinized saline (0.9% NaCl) solution 8 seconds after starting the LiDCO computer. Measurements of CO were obtained in duplicate or triplicate to verify that variation between measurements was < 20%. An interval of at least 2 minutes was allowed between subsequent measurements.

Measurement of CO by NICO—A commercially available monitorm was used to measure CO during both studies.4,5 Measurements were obtained in accordance with the manufacturer's recommendations. Hemoglobin concentration and arterial pressures of carbon dioxide and oxygen required for NICO were determined before CO measurement. A carbon dioxide and volume sensor was connected between the orotracheal tube and anesthetic circuit system. A pulse oximeter was placed on the tongue or lip. Values for CO were determined at 3-minute intervals. This included 60 seconds without rebreathing for baseline determinations of the volume of carbon dioxide eliminated over time, PaCO2, and ETCO2 concentration; 35 seconds of rebreathing during which the volume of carbon dioxide eliminated was decreased, PaCO2 and ETCO2 were increased, and mixed-venous carbon dioxide concentration remained unchanged; and 85 seconds of stabilization and no rebreathing during which all variables returned to baseline values. The rebreathing phase forced each horse to temporarily inhale only a portion of the exhaled gases, and the monitor calculated CO by use of detected differences in carbon dioxide elimination and ETCO2 between the normal and rebreathing state for the following modified Fick equation:

article image

where ΔVCO2 is the difference in carbon dioxide elimination and ETCO2 concentration between the normal state and rebreathing state, and $CaCO2 is the difference in arterial carbon dioxide content between the normal state and rebreathing state.

Experimental design—Designs for the 2 studies4,5 have been described elsewhere. In brief, low, intermediate, and high CO values were achieved in the first study by use of an end-tidal isoflurane concentration of 1.3% to 2.1%, an end-tidal isoflurane concentration of 0.85% to 1.4% and a constant rate IV infusion of dobutaminen (1 to 3 μg/kg/min), and an end-tidal isoflurane concentration of 0.83% to 1% and a constant rate IV infusion of dobutamine (3 to 6 μg/kg/min), respectively. Four foals also received intermittent IV injections of phenylephrineo (total cumulative dose, 1.1 to 1.7 mg) for the highest CO value; phenylephrine was administered after data from the dobutamine phase were recorded. For each CO value, a stable hemodynamic plane of at least 10 minutes was maintained before data collection. At each anesthetic protocol, LiDCO and concurrent NICO measurements as well as SAP, DAP, MAP, and heart rate were recorded.4

Foals in the second study5 were maintained at a steady deep plane of anesthesia by use of an end-tidal isoflurane concentration of 2.0% to 2.5% that causes a hypotensive hemodynamic state. Each foal received 3 treatments in accordance with an orthogonal factorial design; there was at least 24 hours between treatments. Treatment 1 consisted of dobutamine administered at rates of 4 and 8 μg/kg/min, treatment 2 consisted of norepinephrinep administered at rates of 0.3 and 1.0 μg/kg/min, and treatment 3 consisted of vasopressinq administered at rates of 0.3 and 1.0 mU/kg/min. Each drug was always administered at the lower infusion rate first. All treatments were prepared in equal volumes of infusate by dilution in 5% dextrose solution to create appropriate concentrations (dobutamine, 2 mg/mL; norepinephrine, 0.2 mg/mL; and vasopressin, 0.2 U/mL) and were administered by use of a syringe infusion pump.r After a period of at least 15 minutes, LiDCO and NICO measurements as well as blood pressures and heart rate were recorded in the hypotensive state; the vasopressor drug was then administered at the lower infusion rate for a period of at least 15 minutes or until a stable hemodynamic plane was achieved, and all cardiovascular variables were recorded again. Immediately thereafter, the higher infusion rate was initiated in a manner similar to that for the lower infusion rate and cardiovascular variables were recorded for a third time.5

All values for CO were transformed to CI by use of the following equation:

article image

where BW is body weight in kilograms.

Recovery from anesthesia—In both studies,4,5 all instrumentation was removed once the experiments were concluded each day. For the second study, the catheter was allowed to remain in place in the jugular vein with a protective bandage applied to the neck area to avoid repetitive catheterization on subsequent days. Foals were assisted throughout the recovery period and returned to their stalls once fully awake. Foals were observed for evidence of typical suckling activity and behavior during both studies.4,5

Data analysis—The 2 methods were compared by use of a conventional Bland-Altman analysis.6 Bias was defined as the mean value of differences between LiDCO and NICO. Precision (ie, limits of agreement) was defined as 1.96 X SD of the differences and included 95% confidence intervals. For a specific foal with a particular physiologic condition caused by administration of drugs, CO was measured 2 or 3 times concurrently by both the LiDCO and NICO methods. In the case of replicated measurements, additional analyses have been described7 to determine the limits of agreement and account for possible causes of variation. This additional step of repeated, concurrent measurements allows estimation of repeatability of each method and an alternative statistical analysis to determine the limits of agreement. By use of Bland-Altman procedures, the repeatability coefficient for technique x was estimated as follows: sx X (1.96 X √2), where sx is the square root of the residual mean square calculated from an ANOVAs for all individual data points of a particular method (ie, LiDCO or NICO).

In addition to estimation of repeatability, the alternative analysis allows investigators to use all data gathered during investigations.7 Because each foal had the CO value determined 2 or 3 times by each method, an analysis to estimate bias and limits of agreement for an equal number of replicate measurements was used, wherein each foal for a specific physiologic condition was considered a subject. In this case, it is assumed that variances of the means for a given set of individual values are independent of the magnitude of subject means. Therefore, the SD of these measurements for a specific foal was plotted against the mean value of these measurements to ascertain whether the assumption was true. Next, a second assumption of independence that the difference between the means for this data set did not depend on the magnitude of average mean values for a given observation in a particular subject was verified. Therefore, the difference between means was plotted against the mean value of average values.

Once these 2 assumptions were confirmed to be true, the average of the difference in means that provided an estimate of bias between the methods was calculated. To calculate the limits of agreement by use of the entire data set, the following equation7 for an equal number of replicate measurements was used:

article image

where σˆ2d is the variance of the difference between LiDCO and NICO means; s2/d is the observed variance of the differences between within-subject means; mx and my are the number of observations on each subject with methods x (LiDCO) or y (NICO), respectively; and s2xw and s2yw are residual mean square values for the LiDCO and NICO data, respectively, which were calculated for each group separately by use of an ANOVA.t The SEM was calculated as √σˆ2d.

The confidence errors for these limits of agreement were determined by use of the following equation:

article image

where n is number of subjects; s4/d, s4xw, and s4yw correspond to the variables s2/d, s2xw, and s2yw, respectively, for the preceding equation that follow a S2 distribution.

Regression analyses were used to determine correlations and examine the linear relationship between LiDCO and NICO and between LiDCO and heart rate, SAP, DAP, and MAP by use of the recorded value of each variable at the time of a single CO determination. Values of P < 0.05 were considered significant.

Results

Repeatability coefficients for the LiDCO and NICO methods were 32.4 and 40.7 mL/kg/min, respectively. Variances in the mean appeared to be independent of mean values for a specific method (Figure 1). Mean difference (bias) was −17.3 mL/kg/min, and the 95% limits of agreement were −131.3 to 96.7 mL/kg/min (mean ± SD, 114.0 ± 4.2 mL/kg/min; Figure 2).

Figure 1—
Figure 1—

Plots of within-subject SD versus the subject mean for CI measured by use of LiDCO (A) or NICO (B) methods in 18 foals in 2 studies.4,5 A subject was defined as a specific foal for a particular physiologic state. Notice the 1 extreme outlier for NICO, which was considered to be a valid observation.

Citation: American Journal of Veterinary Research 68, 2; 10.2460/ajvr.68.2.141

Figure 2—
Figure 2—

Bland-Altman plot of subject bias and precision (ie, limits of agreement; 1.96 X SD) determined by use of replicated measurements for 18 foals in 2 studies.4,5 The solid horizontal line indicates the mean bias of the measurements, the dotted horizontal lines depict the limits of agreement, and the dashed lines around each dotted line represent the 95% confidence intervals of the limits of agreement. See Figure 1 for remainder of key.

Citation: American Journal of Veterinary Research 68, 2; 10.2460/ajvr.68.2.141

The collated data yielded 217 comparisons. There was good correlation between LiDCO and NICO (r = 0.77; Figure 3). Mean ± SD LiDCO and NICO values from 217 measurements were 138 ± 62 mL/kg/min (range, 40 to 381 mL/kg/min) and 154 ± 55 mL/kg/min (range, 54 to 358 mL/kg/min), respectively. Mean of the differences of LiDCO minus NICO was 4.37 + (0.87 X NICO).

Figure 3—
Figure 3—

Linear regression for a wide range of CI values measured concurrently by LiDCO and NICO methods in 18 anesthetized foals in 2 studies.4,5 The solid line indicates the best fit, and dashed lines indicate 95% confidence intervals. There was good correlation (r = 0.77) between the methods. Equation for the slope of the line was as follows: y = 4.37 + 0.87x, which indicates that LiDCO = 4.37 + [0.87 X NICO]).

Citation: American Journal of Veterinary Research 68, 2; 10.2460/ajvr.68.2.141

In the first study,4 107 comparisons were made between the 2 methods. Eight comparisons were excluded because variation was > 20% between the LiDCO measurements or there were technical errors at the time of determination. For all CO determinations, there was good correlation (r = 0.63) between the 2 methods. Mean ± SD LiDCO and NICO values from 99 measurements were 133 ± 43 mL/kg/min (range, 64 to 237 mL/kg/min) and 146 ± 34 mL/kg/min (57 to 209 mL/kg/min), respectively. Mean of the differences for LiDCO minus NICO was −17.81 + (0.78 X NICO). Magnitude of the limits of agreement of the differences between LiDCO and NICO was 66.5 mL/kg/min (−80.1 to 52.8 mL/kg/min), with a mean difference (bias) of −13.7 mL/kg/min.

In the second study,5 2 foals had cardiac arrest after collection of baseline data in the hypotensive state. They were successfully resuscitated but were excluded from the remainder of the study. Initial data points for both foals were included because they were collected before the incident.

For the second study,5 120 comparisons were made between the 2 methods. Two comparisons were excluded because they equaled or exceeded the maximum value on the NICO monitor (19.9 L/min). For all CO determinations, there was good correlation (r = 0.81) between the 2 methods. Mean ± SD LiDCO and NICO values from 118 measurements were 143 ± 74 mL/kg/min (range, 40 to 381 mL/kg/min) and 160 ± 68 mL/kg/min (range, 54 to 358 mL/kg/min), respectively. Mean of the differences for LiDCO minus NICO was −0.06 + (0.89 X NICO). Magnitude of the limits of agreement of the differences between LIDCO and NICO was 87.5 mL/kg/min (−105.2 to 69.7 mL/kg/min), with a mean difference (bias) of −17.8 mL/kg/min.

The strongest correlation between CI determined by LiDCO and the other cardiovascular variables measured simultaneously was for heart rate (r = 0.62). There were weak correlations between CI determined by LiDCO and SAP (r = 0.41), DAP (r = 0.25), and MAP (r = 0.34).

Discussion

Methods for CO measurement that are minimally invasive, such as NICO, are optimal for monitoring neonatal foals, but they have not been validated for use in this species. The LiDCO method is accurate and can be used as an alternative to more traditional methods, including thermodilution, in foals and other species.3,8-10

Bias and limits of agreement were similar for analysis conducted by use of nonreplicated and replicated data. Replicates were 2 or more measurements on the same patient obtained in identical conditions in quick succession, with an expected mean difference between them of 0.7 When 1 method has poor repeatability so that there is considerable variation in the replicated measurements, the agreement between the 2 methods will be poor. Given the relative similarity of values for the limits of agreement, both methods appeared to be sufficiently precise to allow repeated data that are valid. The limits of agreement were approximately 2- to 3-fold greater than the repeatability coefficients. When the limits of agreement are dependent only on the repeatability of measurements, then the limits of agreement should be equal to the repeatability coefficients. Because the limits of agreement were wider than the repeatability, then there must have been some other factor that decreased agreement between the methods. For example, it is conceivable that the NICO device was designed such that it would require a correction factor for intrapulmonary shunt flow, a value that may cause overestimation or underestimation of CO when the correction factor varies from true intrapulmonary shunt flow.11 In another study,12 investigators determined that the LiDCO measurement increased with sequential lithium administration for determination of CO as a result of increases in lithium concentrations.

In addition to inaccuracy attributable to these factors, other unrecognized errors could have contributed to the gap in repeatability values and limits of agreement. Variations between the 2 methods were also possible sources of error because in the first study,4 but not in the second study,5 ETCO2 concentrations were manipulated to remain within a specific range, which may have affected the accuracy of NICO.

Objectives differed for the 2 studies that provided the data, but each provided useful scenarios that resemble aspects of clinical situations encountered in anesthetized foals. These include depressed and improved cardiovascular performance in response to anesthetics and inotropic or vasopressor drugs. Investigators in the first study4 manipulated anesthetic depth (0.69 to 1.75 MAC)u in combination with administration of inotropic drugs and vasopressors to induce various degrees of cardiovascular function. This is in contrast with the second study5 in which researchers investigated the ability of inotropic drugs and vasopressors to counteract induced cardiodepressive effects for constant administration of a high end-tidal concentration of isoflurane (2.4 to 3.0 MAC).

The range of CI induced in the 2 studies4,5 included values (40 to 381 mL/kg/min) for an age group (ie, neonatal foals) in which reported1 CI values for clinically normal conscious animals are 197 to 234 mL/kg/min. Thus, we were able to compare LiDCO and NICO methods over a wide range of values. In the first study,4 data for 30 averaged pairs of LiDCO-NICO comparisons were reported; however, in the study reported here, those measurements for each method were used individually and not as replicated averaged pairs. Other measurements recorded at other time intervals in that study4 were also included, which resulted in 99 comparisons. In addition, it was determined in the first study4 that CO influenced NICO measurements; therefore, those data were reported for low, intermediate, and high CO values. In the study reported here, overall bias and precision of the 99 individual comparisons were calculated, in addition to the 118 individual comparisons of the second study.5

The comparison between LiDCO and NICO in each of those 2 studies4,5 revealed mean differences of −14 to −18 mL/kg/min and limits of agreement of −105 to 70 mL/kg/min between LiDCO and NICO. The negative value for bias indicated that use of NICO would overestimate the LiDCO values. Analysis of data from the first study4 revealed that the negative value for bias, and therefore overestimation for NICO, tended to decrease progressively as CI increased toward more physiologic values because maximum CI values achieved by use of the LiDCO method in that study were 237 mL/kg/min. Studies in pigs13 and sheep14 have also revealed overestimation at low CI values and underestimation at high CI values, whereas in dogs, NICO slightly underestimates LiDCO at all CI values, although the difference is larger at higher CI values.15

It was suggested in 1 study14 that the increase in mixed-venous PaCO2 is a result of recirculation during hyperdynamic states (ie, high CI), which overestimates theETCO2 concentration and affects the assumption for NICO that the difference in partial pressures between end-capillary carbon dioxide and ETCO2 is constant during rebreathing and nonrebreathing states. The underestimation of CI by NICO is more evident as CI increases.14 Conversely, during hypodynamic states for NICO, the time during the rebreathing states needed to achieve equilibrium between the partial pressures of end-capillary carbon dioxide and ETCO2 is insufficient, which leads to underestimation of the partial pressure of end-capillary carbon dioxide and a smaller difference between end-capillary carbon dioxide and ETCO2 partial pressures.14

In the study reported here, values generally became scattered as CI increased, which was most obvious when CI exceeded 200 mL/kg/min. Similar results have been reported15 for LiDCO and NICO comparisons in dogs at CI values that exceed 110 mL/kg/min. Typical values for CI in conscious foals and dogs are close to the values in which scattering was initially detected in the study reported here and another study.15 It is likely that the hyperdynamic state induced by inotropic drugs, which results in a higher degree of pulmonary shunting and lower difference between venous PCO2 and Paco2, decreased the accuracy for NICO, similar to results in other reports.13,14,16

Cardiovascular depression induced by inhalant anesthetics reduces CI and may affect pulmonary blood flow. Use of inotropic and vasopressors to counteract depressive effects may also affect pulmonary blood flow. The acute nature of changes induced by low blood flow and hyperdynamic circulatory states for the methods used in the 2 studies4,5 as well as in another study may have contributed to decreased accuracy of NICO. The correlation between NICO and aortic blood flow determined by use of a periaortic transit-time flow probe in pigs13 was similar to the correlation obtained between NICO and LiDCO (r = 0.77) for the study reported here but was less than the correlation between those 2 methods for a similar study15 in dogs (r = 0.88).

The NICO method should be limited to patients that can tolerate increases in PaCO2 that result from the forced partial rebreathing needed for this method. In addition, mechanical ventilation increases accuracy and aids in maintaining ETCO2 concentrations. There were differences in the methods for the studies because ETCO2 pressures were maintained between 40 and 50 mm Hg throughout the first study4 but not during the second study.5 In the second study, investigators assessed the effects of several inotropic drugs or vasopressors on gastric carbon dioxide tonometry during hypotension; therefore, no attempts were made to alter ETCO2 values. However, mean ETCO2 values did not exceed 65 mm Hg in the second study. Concentrations > 65 mm Hg measured during the baseline cycle or > 80 mm Hg during the rebreathing cycle of NICO can interfere with accuracy of the monitor.17 In addition, tidal volume (10 to 15 mL/kg) and minute ventilation (rate of 8 to 10 breaths/min) were maintained constant in all foals by means of mechanical ventilation to avoid negative effects on accuracy of NICO attributable to low tidal volumes, reduced minute ventilation, and spontaneous respiration.17,18

Methods for determination of CO are important when evaluating cardiovascular performance in awake and anesthetized patients. Measurement of CO is less commonly performed, compared with the frequency for other variables (such as measurement of blood pressure), primarily because of the more invasive nature and the need for instrumentation of patients to obtain CO determinations. Blood pressure is considered a reliable indicator of cardiovascular function, and blood pressure is typically monitored by direct or indirect methods during anesthesia. In the study reported here, CI had a poor correlation with blood pressure values but a better correlation with heart rate. Similar results have been reported15 in dogs. Cardiac performance should be interpreted with caution when based on blood pressure alone because systemic vascular resistance determines blood pressure to a great extent, but it adversely affects CI. These effects have been reported19,20 in adult horses ventilated during halothane- or isoflurane-induced anesthesia in which CI had an inverse relationship with MAP, which was attributed to changes in systemic vascular resistance.

The NICO method is an ideal noninvasive technique for determination of CO in anesthetized foals that are mechanically ventilated. The method is limited by the need to ventilate patients, the necessity for tolerance to a higher ETCO2 concentration during the rebreathing cycle, and the fact a 3-minute cycle necessary to obtain a new measurement may delay the detection of a substantial change in CO. However, because it is easy to use, is minimally invasive, and performed well in the study reported here, NICO compares well with LiDCO, although overestimation for was evident at low values of CI.

ABBREVIATIONS

CO

Cardiac output

LiDCO

Lithium dilution CO

NICO

Noninvasive CO measured by partial carbon dioxide rebreathing

ETCO2

End-tidal carbon dioxide

SAP

Systolic arterial pressure

DAP

Diastolic arterial pressure

MAP

Mean arterial pressure

CI

Cardiac index

MAC

Minimum alveolar concentration

a.

DVM Stat, Corp for Advanced Applications, Newburg, Wis.

b.

Anased, Akorn Inc, Decatur, Ill.

c.

Valium, Abbott Laboratories, North Chicago, Ill.

d.

VetaKet, Phoenix Scientific Inc, St Joseph, Mo.

e.

IsoFlo, Abbott Laboratories, North Chicago, Ill.

f.

S/5, Datex-Ohmeda Division, Helsinki, Finland.

g.

DOT-34 NRC 300/375 M1014, Datex-Ohmeda Division, Helsinki, Finland.

h.

Plasmalyte 148 with 5% dextrose, Baxter Healthcare Corp, Deerfield, Ill.

i.

LiDCO cardiac computer CM 31-01, LIDCO Ltd, London, UK.

j.

ABL system 605/600, Radiometer Medical A/S, Copenhagen, Denmark.

k.

LiDCO sensor, LiDCO Ltd, London, UK.

l.

Lithium chloride, LiDCO Ltd, London, UK.

m.

NICO, Novametrix Medical Systems Inc, Wallingford, Conn.

n.

Dobutamine, Bedford Laboratories, Bedford, Ohio.

o.

Phenylephrine, Bedford Laboratories, Bedford, Ohio.

p.

Levophed, Abbott Laboratories, North Chicago, Ill.

q.

Vasopressin, American Regent Inc, Shirley, NY.

r.

Medfusion model 2010i syringe pump, MedexInc, Duluth, Ga.

s.

SigmaStat for Windows, version 2.03, SPSS Inc, Chicago, Ill.

t.

ANOVA, SPSS for Windows, version 14.0, SPSS Inc, Chicago, Ill.

u.

Dunlop CI, Hodgson DS, Grandy JL, et al. The MAC of isoflurane in foals (abstr). Vet Surg 1988;18:249.

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Contributor Notes

Dr. Valverde's present address is Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

Supported by the Florida Thoroughbred Breeders' and Owners' Association.

Presented in part at the American College of Veterinary Anesthesiologists, the International Veterinary Academy of Pain Management, and the Academy of Veterinary Technician Anesthetists Meeting, Phoenix, October 2004; and at the 9th World Congress of Veterinary Anesthesia, Santos, Brazil, October 2006.

Address correspondence to Dr. Valverde.