Arterial Pressure–Based Cardiac Output Assessment

EMERGING TECHNOLOGY Gerard R. Manecke, Jr, MD Marco Ranucci, MD Section Editors

Arterial Pressure–Based Cardiac Output Assessment Timothy M. Maus, MD, and Daniel E. Lee, MD, PhD

T

HE ASSESSMENT OF cardiac output (CO) may be useful in the management of critically ill patients as well as healthy patients undergoing major surgery.1 Historically, CO determinations have been made with the use of the pulmonary artery catheter (PAC). This method is accurate; however, it has several disadvantages. In addition to the risks of central venous access, there are risks of the right-heart catheterization, with potential for catastrophic complications.2,3 Pulmonary artery thermodilution methods have several assumptions: flow is continuous during the CO determination, complete mixing of the injectate occurs, and there is no loss of indicator outside of the system. These assumptions may lead to inaccurate CO determinations. Also, many PAC thermodilution systems function with intermittent boluses of injectate leading to discontinuous monitoring of CO. These disadvantages, along with the realization that fluid optimization, even in healthy patients undergoing major surgery, improve outcomes have led to the search for alternative methods of CO determination. Particularly attractive among the resulting technologies are the arterial pressure– based cardiac output (APCO) systems. APCO determinations have been challenged with the difficulty in deriving the amount of flow in relation to the change in pressure of the arterial waveform. This requires knowledge of the interdependent variables of aortic impedance, arterial compliance, and peripheral vascular resistance. Several algorithms for waveform analysis have been developed; some are currently available as commercially-produced monitors. The algorithms may include the area of the systolic pressure curve analysis, pulse-power analysis, standard deviation of the pressure trace, or pulse-contour methods to determine flow. Patient data characteristics, waveform morphology, and/or calibration with independent CO measurements are used to account for patient-specific aortic impedance, arterial com-

pliance, and peripheral vascular resistance. APCO systems are discussed in detail including how they derive flow from the arterial pressure trace and thereby determine cardiac output. The purpose of this review is to present, in detail, the current available APCO technologies as well as some experimental ones.

From the Department of Anesthesiology, University of California, San Diego, CA. Address reprint requests to Timothy M. Maus, MD, Department of Anesthesiology, University of California, San Diego, 200 West Arbor Drive, Mail Stop 8770, San Diego, CA 92103. E-mail: tmaus@ ucsd.edu © 2008 Elsevier Inc. All rights reserved. 1053-0770/08/2203-0025$34.00/0 doi:10.1053/j.jvca.2008.03.012 Key words: cardiac output measurement, arterial pressure– based cardiac output, thermodilution cardiac output

where lithium dose is in mmol, area is the integral of the primary curve, and PCV is the packed cell volume that may be calculated as hemoglobin concentration (g/dL)/34; the PCV correction is necessary because lithium is distributed in the plasma and not into red cells.4 The PulseCO software system uses pulse power, a technique that is not morphology based as in pulse-contour methods, rather on the assumption that the net power change in a heartbeat is the balance between the SV of blood entering the arterial tree minus the blood loss to the periphery during the heartbeat.

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LiDCO PLUS HEMODYNAMIC MONITOR (LiDCO LTD, CAMBRIDGE, UK)

The LiDCO plus Hemodynamic Monitor is a combination of 2 systems: the LiDCO lithium indicator dilution CO system and the PulseCO real-time arterial waveform monitor both produced by LiDCO Ltd. The PulseCO System calculates continuous CO from the arterial blood pressure trace after calibration with the LiDCO CO determination. The system requires a pre-existing arterial catheter for both pressure wave and lithium dilution curve analysis as well as venous access for small-dose lithium administration. Current manufacturer recommendations include a calibration of the continuous CO determination with lithium dilution CO every 8 hours. Hemodynamic variables including CO, cardiac index (CI), systemic vascular resistance (SVR), stroke volume (SV), SV index, SV variation (SVV), systolic-pressure variation, and pulse-pressure variation may all be derived from the LiDCO plus Hemodynamic Monitor. The LiDCO plus system is attached to the patient such that a lithium sensing-electrode is connected in line to an existing arterial catheter as well as a pump device that draws blood past the sensor at a steady rate (4 mL/h). Via a central or peripherally inserted venous access, a pharmacologically insignificant dose of lithium is administered to the patient resulting in a lithium concentration-time curve at the arterial-sensing electrode. The LiDCO monitor then calculates the CO from the area under the primary dilution curve via the formula: CO ⫽ 共lithium dose · 60兲 ⁄ 关area · 共1 ⫺ PCV兲兴 ,

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The net power change then is correlated to net flow given a correction for compliance and calibration.5 Autocorrelation of the derived volume-time waveform involves subtracting the derived arterial blood volume from the volume-time waveform, resulting in a sine-like waveform, which is subsequently squared to produce a double waveform. The root mean square, the square root of the mean of this waveform, produces a net effective beat power factor, which is proportional to the nominal SV. Autocorrelation (continually shifting the wave until there is a tau shift) of the waveform determines the beat duration.4 By using the entire pressure waveform rather than just the systolic portion of the curve, the PulseCO system incorporates the influence of peripheral resistance (the reflected wave from the periphery). Once provided with the nominal SV, beat duration, and calibration from the LiDCO system, SV and thus continuous CO are determined. Separate from the PulseCO and LiDCO plus Hemodynamic Monitor, lithium dilution CO determination has been validated in numerous studies against the clinically accepted gold standard of pulmonary artery thermodilution with acceptable levels of bias and precision.6,7 Both the peripheral and central injection of lithium have been validated as an acceptable method of CO measurement.8 Lastly, the pulse-power analysis used in the LiDCO plus system also has been validated against both lithium dilution CO and PAC techniques.9,10 The function of the LiDCO plus system is limited in patients on pharmacologic doses of lithium secondary to background noise from the therapeutic lithium levels as well as in patients treated with certain muscle relaxants, including both depolarizing and nondepolarizing varieties with quaternary ammonium ions, which result in a drift in the lithium sensor. However, because the system analyzes net power, the effect of arterial catheter dampening on the cardiac output determinations is minimized. In summary, the LiDCO plus system provides continuous CO monitoring along with other hemodynamic variable determinations such as SVV from typical monitoring catheters of critically ill patients. PiCCO PLUS (PULSION MEDICAL SYSTEMS AG, MUNICH, GERMANY)/PiCCO CONTINUOUS CARDIAC OUTPUT MONITORING (PHILIPS MEDICAL SYSTEMS, ANDOVER, MA)

Pulse-induced continuous cardiac output (PiCCO) developed by Pulsion Medical Systems is the pulse-contour analysis and transpulmonary thermodilution system that is incorporated into the PiCCO plus system by Pulsion Medical System and the PiCCO continuous CO monitor produced by Philips Medical Systems. The 2 systems use a proprietary thermistor-tipped arterial catheter placed in the femoral, brachial, axillary, or radial artery (50-mm long catheter) that functions to provide transpulmonary thermodilution as well as analysis of the arterial pressure wave for continuous CO monitoring. An existing central venous catheter is required to administer the injectate solution for thermodilution analysis and pulse-contour analysis calibration. The PiCCO technology provides additional hemodynamic variables including SV, SVV, SVR, transpulmonary CO, intrathoracic blood volume, and cardiac function index from intermittent thermodilution. The PiCCO system by Philips has the ability to integrate into current Philips-branded

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IntelliVue monitors, whereas the PiCCO plus is a stand-alone monitor that incorporates additional hemodynamic variables such as global end-diastolic volume, intrathoracic blood volume, and global ejection fraction. PiCCO uses 2 techniques to provide continuous CO determinations, pulse-contour analysis in conjunction with transpulmonary thermodilution calibration. An injectate temperature sensor is connected to an in situ central venous catheter and provides the system with accurate injection temperatures. A thermodilution arterial catheter is placed in a central artery and connects to the PiCCO system through both a temperature interface cable for transpulmonary thermodilution and via a pressure transducer for pulse-contour analysis. After central venous injection of the saline, cold or room temperature, the thermistor-tipped arterial catheter measures the temperature change in relation to time. The resultant thermodilution curve is used to calculate cardiac output via the following formula11: CO TDa⫽关共Tb ⫺ Ti兲 · Vi · K兴 ⁄

共兰 ⌬T · dt兲 , b

where Tb is the blood temperature, Ti is the injectate temperature, Vi is the injectate volume, 兰⌬Tb · dt is the area under the thermodilution curve, and K is the correction constant consisting of specific weight and specific heat of blood and injectate. For the PiCCO plus system, volumetric parameters are also calculated by using further analysis of the thermodilution curve including mean transit time and downslope time. The pulse-contour algorithm developed by Wesseling et al12 serves as the basis for the analysis software for PiCCO. For the first versions of the software, SV essentially was determined by calculating the area under the systolic portion of the arterial waveform (Asys) and dividing by the aortic impedance (Zao). The SV multiplied by heart rate then yielded CO. Calibration with thermodilution adjusts for differences in interpatient aortic impedance and provides the variable Zao to the following formula11: CO ⫽ (heart rate ⫻ Asys)/Zao. Newer versions of the PiCCO software use a more sophisticated formula that also analyzes the shape of the arterial pressure waveform and accounts for the influence of individual aortic compliance and peripheral vascular resistance. These changes help to improve accuracy by relating the dynamic physical characteristics of the aorta during systolic ejection and diastolic outflow. These updates to the software are based on the concept that during systole, more blood enters the aorta than exits, relating to aortic compliance, whereas the remaining positive balance of blood then leaves the aorta during diastolic flow in relation to compliance, peripheral vascular resistance, and blood pressure. The relation of the individual patient thermodilution calibration, measurement of systolic pressure curve area, compliance, and the shape of the pressure curve is shown in the following formula: PCCO ⫽ cal · HR ·

兰 关P共t兲 ⁄ SVR ⫹ C共p兲 · dP ⁄ dt兴dt,

where cal is the patient-specific calibration factor determined with thermodilution, HR is the heart rate, P(t)/SVR represents the area of the pressure curve, C(p) represents arterial compliance, and dP/dt represents the shape of the pressure curve.

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The shape of the pressure curve, as represented by the change of pressure over the change of time, identifies the dicrotic notch and assesses the slope after the dicrotic notch, which is affected by the compliance of the aorta and peripheral vascular resistance. Similar to prior versions of the PiCCO software, calibration aids in determining an individual patient’s compliance.13 Independent of the pulse-contour analysis, the transpulmonary thermodilution method of CO determination has been validated against both pulmonary artery thermodilution as well as the Fick method.14-16 The pulse-contour analysis also has been validated in numerous studies particularly against pulmonary artery thermodilution with acceptable levels of bias and precision.11,13 Potential limitations of the PiCCO system include the specific need for central access for injectate administration for proper calibration. The system also requires a centrally placed arterial access either via femoral, brachial, axillary, or long catheter radial routes with proprietary catheters. Advantages include the independence from the respiratory cycle with transpulmonary thermodilution techniques, the additional volumetric parameters provided by the PiCCO plus system, and lastly the validation for use in children. The PiCCO system is therefore able to reliably monitor trends in CO without the need for pulmonary artery catheterization. FLOTRAC SENSOR AND VIGILIO MONITOR (EDWARDS LIFESCIENCES LLC, IRVINE, CA)

The Edwards Lifesciences minimally invasive monitoring system involves the FloTrac sensor, a specialized transducer that preprocesses the arterial waveform, and the Vigileo monitor, a stand-alone display unit that applies the proprietary algorithm to provide CO on a continuous basis. The system is attached to an existing peripheral arterial catheter with the advantage of not requiring calibration with an alternative CO determination. The algorithm along with the input of patient characteristics such as age, sex, height, and weight have the ability to assess and detect changes in the individual patient’s arterial compliance and peripheral vascular resistance via waveform morphologic analysis. The monitor provides hemodynamic variables of CO, CI, SV, SV index, SVV and with the input of a standard central venous catheter, calculations of systemic vascular resistance and index are provided. The FloTrac sensor once attached to the patient’s in situ arterial catheter is attached via data cables to both the Vigileo monitor for digital wave processing and to a standard monitor for pressure monitoring. If a central catheter is present, a slave cable may be attached from the standard monitor to the Vigileo for SVR calculations. Once patient data such as age, sex, and BSA are entered and the system is zeroed, hemodynamic variables will be provided at 20-second intervals based on continuous monitoring of the arterial waveform. The system calculates the CO using arterial pulsatility, resistance, and compliance, according to the following formula17: APCO ⫽ PR · sd共AP兲 · ␹ , where PR represents pulse rate, sd(AP) represents pulsatility using the standard deviation of the arterial pressure wave over a 20-second interval, and ␹ represents a constant that quantifies

arterial compliance and peripheral vascular resistance. Pulse rate is computed from the time period of beats identified by the upslope of waveforms. The standard deviation of the entire arterial pressure wave is sampled at 100 Hz to provide 2,000 data points every 20 seconds. The standard deviation of these data points is proportional to the pulse pressure and therefore to the SV. An increase in the variance of the data points indicates an increase in pulse pressure and therefore an increase in SV. Lastly, the ␹ constant is derived from the patient data characteristics of age, sex, height, weight, and waveform morphology. The patient characteristics influence the compliance of the aorta originally quantified with human cadavers by Langewouters et al18 such that factors of being younger, male, or a higher body surface area (BSA) are correlated with a more compliant aorta than characteristics of being older, female, or of a lower BSA. The Langewouters’ criteria provide a baseline determination of the patient’s vascular tone; however, the algorithm further analyzes the waveform for the real time effects of vascular tone. In particular, changes in mean arterial pressure, skewness (slope exhibited on the rise of the waveform), and kurtosis (the degree of flatness or wideness) indicate changes in vascular tone. An increase in tone is calculated as a decrease in ␹ such that a decrease in ␹ value will decrease the influence of pulse pressure (pulsatility) in CO determination. Accounting for real-time changes in vascular tone allows the Vigileo to reliably calculate continuous CO without calibration providing hemodynamic variables at 20-second intervals with a recalculation of ␹ every 1 minute. The FloTrac sensor is a relatively new product released for clinical use in 2005; however, several studies have validated its clinical agreement to the accepted gold standard method of CO determination, PAC thermodilution. Manecke and Auger19 and McGee and Janvier20 have validated the system against intermittent and continuous PAC thermodilution in postoperative cardiac surgical patients and in a multicenter study of medical and surgical patients, respectively. Limitations of the FloTrac/Vigileo system include possible inaccuracy in the setting of arterial wave artifacts such as air in or kinking of the arterial catheter tubing, aortic regurgitation, and use of an intra-aortic balloon pump. The FloTrac sensor also is currently not validated or labeled for use in pediatric populations. The system, however, offers the distinct advantage of providing continuous CO and other hemodynamic variables solely with a peripherally inserted arterial catheter without the need for manual calibration. Like other arterial pressure– based systems, the FloTrac/Vigileo system provides continuous SVV for potential assessment and guidance of fluid management. FINOMETER WITH MODELFLOW METHODOLOGY (FINAPRES MEDICAL SYSTEMS BV, AMSTERDAM, THE NETHERLANDS)

The Finometer is a noninvasive blood pressure measurement monitor that with proprietary ModelFlow methodology waveform analysis provides beat-to-beat CO monitoring. The system can operate noninvasively by using the volume-clamp method of obtaining finger arterial pressure tracings with the Physiocal algorithm to periodically correct the system for changes such as hematocrit, physiologic stress, or smooth muscle tone. Return-

ARTERIAL PRESSURE–BASED CO ASSESSMENT

to-flow calibration uses a brachial cuff in conjunction with the finger cuff to provide accurate brachial level arterial pressure waveforms and values from the finger arterial trace. Using a simulated 3-element arterial model of flow as previously described by Wesseling et al,12 the ModelFlow method provides continuous CO monitoring. The system also allows an externally provided arterial waveform such as from an intra-arterial catheter to be analyzed by ModelFlow. The Finometer is offered in 3 forms: Finometer MIDI, which offers CO trending; Finometer Pro, which includes the brachial cuff– based returnto-flow calibration; and the Portopres, a battery-operated portable version of the system. The Finometer provides beat-tobeat parameters inclusive of CO, SV, SVR, pulse-rate variability, and baroreflex sensitivity. The Finometer system includes a finger-pressure cuff with an inflatable bladder as well as a photoplethysmography light source and a detector for application of the volume-clamp method. A front-end unit contains a servo-controlled pressure device for applying the rapidly changing pressures to the finger-pressure cuff. The front-end unit, in turn, is connected to the Finometer for finger arterial tracing determination, brachial pressure derivations, and CO determinations. The volume-clamp method uses the inflatable finger-pressure cuff such that the diameter of the artery under the cuff is kept constant despite the changes in arterial pressure.21 These changes in diameter are detected via the infrared photoplethymograth light source and detector. During the cardiac cycle, a change in the diameter of the artery is detected, and the servocontroller system responds rapidly to prevent the diameter change. If the diameter remains unchanged, there is a remaining zero transmural pressure, and therefore the finger-cuff pressure equals the intra-arterial pressure. The Physiocal calibration examines the plethysmogram at a number of continuous pressure levels to determine the arterial diameter with zero transmural pressure. This calibration requires temporary interruption of the arterial pressure trace. The finger arterial pressure tends to differ from the brachial pressure with a slightly higher systolic pressure and lower mean and diastolic pressures related to pulse-pressure amplification and pressure decay, respectively.21 The application of an inverse antiresonance model, using the 8-Hz resonance for the frequency transfer function from brachial to finger arterial pressures, allows the reconstruction of a brachial artery waveform that tracks actual brachial pressures. This, however, does not correlate the finger–to– brachial pressure in magnitude, and therefore return-to-flow calibration uses a brachial cuff to apply a correction. Beat-to-beat SVs and therefore CO determinations in the Finometer use the Modelflow method of simulating a nonlinear 3-element model of aortic input impedance as described by Wesseling et al.12 The system uses the integral of the aortic flow under the systolic portion of the arterial pressure curve in conjunction with a model estimation of aortic impedance, compliance, and peripheral vascular resistance for a given pressure. Using data from Langewouters et al18,22 on the nonlinear nature and viscoelasticity of human aortas in response to various pressures including differences for age, sex, height, and weight, Wesseling et al used the model to estimate the vascular impedance and compliance.

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The model uses the estimated aortic impedance and arterial compliance as its major determinations of aortic flow.21 The impedance relates to the opposition by the aorta to pulsatile inflow from the heart. The compliance relates to the aortic pressure rise for a given amount of blood entering the system relating to the elasticity of the aorta. Peripheral vascular resistance relates to the ease with which the blood in the aorta flows to the periphery. The model calculates the peripheral resistance as modeled flow divided by arterial pressure. Therefore, model flow is determined by simulating the behavior of the model under the applied arterial pressure waveform, using impedance and compliance as a nonlinear function of instantaneous pressure.12 The integral of model flow during systole provides SV, which multiplied by heart rate provides the CO determination. Numerous studies have evaluated the Finometer and Modelflow for use in clinical settings. Evaluating the system against thermodilution from a PAC, Remmen et al23 found the Modelflow CO determinations from finger arterial pressure tracings to be inaccurate. Jansen et al24 recommended calibration with an independent method after comparing the system with thermodilution. When compared with CO calculations from intraarterial catheters, the finger-pressure determinations also were found to be inaccurate with recommendations for calibrating with an independent method.25 However, when calibrated with another CO determination, the Modelflow CO values from finger-pulse pressures were found to be reliable and accurate.26 The Finometer systems use a peripheral arterial trace and therefore may be limited in settings of severe vasoconstriction, cold fingers, and Raynaud’s syndrome.27 The cuffs are designed in sizes down to approximately 6 years of age, and therefore the system is limited in patients of very young age. However, there is the distinct advantage of being able to trend CO completely noninvasively through the use of finger and brachial arterial pressure cuffs. Overall, the system has the ability to trend changes in CO; however, if absolute values are desired, a calibration with another CO determination is necessary. THE PRESSURE-RECORDING ANALYTIC METHOD

The pressure-recording analytic method (PRAM) is a new method of determining continuous CO changes from the arterial pressure wave via mathematic analysis of the arterial pressure profile changes. The method analyzes the arterial pressure wave solely from a standard peripheral or centrally inserted arterial catheter without need for independent CO calibration. The method is based purely on waveform analysis without use of retrospective ex vivo aortic measurements related to aortic impedance and compliance. PRAM analyzes the entire waveform including both the pulsatile portion involving cardiac ejection, compliance, and impedance as well as the continuous diastolic portion of flow related to peripheral vascular resistance. The technique recognizes that volume changes in the arterial system are related primarily to the radial expansion of the system in response to blood pressure changes. Involved in this process are the force of cardiac ejection, aortic impedance to inflow into the aorta, arterial compliance that elastically stores energy of the cardiac ejection, and lastly the vascular resistance providing retrograde reflections. These values are interdependent and are obtained in

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the PRAM technique via morphologic analysis of the arterial pressure waveform. SV is calculated as SV ⫽ A/(P/t · K), where A is the area under the systolic portion of the curve, P/t is the analysis of the entire pressure wave as the change in pressure with time, and K is the dimensional factor inversely related to the instantaneous acceleration of the vessel crosssectional area. K is calculated as a ratio of expected and measured mean blood pressure. The numerator, expected blood pressure, is a constant derived from expected blood pressures under physiologic conditions, whereas the denominator is the measured blood pressure, therefore providing a measure of variation from unity. K provides a correction for the deviation from normal physiologic conditions. P/t is the summation of multiple portions of the analysis of the pressure over the cardiac cycle. The factor assumes that peak systolic pressure and the pressure of the dichrotic notch are points of dynamic equilibrium in regards to flow in the arterial system. The differences in systolic and diastolic pressures over time relate to the impulse of the cardiac ejection. The pressure at the dichrotic notch over diastolic time relates to the forces involved in the diastolic continuous runoff. With changes in peripheral vascular resistance, the time of the dichrotic notch may be delayed, and therefore a third summation term is involved in the calculation of P/t. This involves the maximum value of the first derivative of the pressure curve between peak systolic and dichrotic notch values, which accounts for the changes in the morphology of the pressure wave.28 Therefore, with the calculation of the area under the systolic portion of the pressure curve, the summation of terms involved in the analysis of the entire pressure-wave curve, and the determination of variation from physiologic conditions, the previously given formula yields calculation of SV. Multiplying SV by heart rate yields CO. The pressure-recording analytic method has been validated against the accepted gold standard, pulmonary artery catheter thermodilution, in the original description of the method by Romano and Pistolesi in 2002.28 Subsequent studies include the evaluation of cardiac surgery patients, with acceptable bias and precision in comparison to both thermodilution as well as extracorporeal circulation CO values.29,30 Because PRAM has

the ability to calculate CO during both the pulsatile systolic ejection and the continuous flow of diastolic runoff, the method continues to calculate accurate CO during the arterial radial expansion secondary to roller pump output during cardiopulmonary bypass.30 The method is relatively new and at the time of this writing does not exist as a commercially available product. The system has been validated against thermodilution; however, it may require further testing in settings of hemodynamic instability. PRAM does offer the benefit of determining CO solely from a radial artery catheter without need for calibration with an independent method. There is the additional benefit of potentially monitoring changes in CO while transitioning from extracorporeal to spontaneous circulation. ESTIMATED CONTINUOUS CO

Ishihara et al31 have described a new technique for obtaining continuous CO values using a combination of pulse-contour analysis and pulse-wave transit time with routine monitors of an arterial catheter, electrocardiogram, and pulse oximetry. Initial calibration with an alternative method of CO determination is required with the initial description using PAC thermodilution. The method was noted to be able to trend CO but was not interchangeable with PAC thermodilution. CONCLUSION

Currently, the clinical gold standard for CO measurements is pulmonary artery catheter thermodilution; however, APCO systems offer an alternative potentially less invasive method for CO assessment. Newer algorithms and technologies allow the monitoring of CO on a continuous basis with clinically acceptable bias and precision when compared with PAC thermodilution and other accepted methods of CO measurement. In addition to continuous CO, many of these systems offer additional hemodynamic variables including SVV, which may prove to be helpful in fluid management in critically ill patients. As with any new technology, further experience is needed in multiple clinical scenarios with varying degrees of hemodynamic instability to further define the benefits and limitations of the systems. The arterial pressure– based CO systems are clinically reliable for continuous CO monitoring.

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11. Godje O, Hoke K, Goetz AE, et al: Reliability of a new algorithm for continuous cardiac output determination by pulse-contour analysis during hemodynamic instability. Crit Care Med 30:52-58, 2002 12. Wesseling KH, Jansen JR, Settels JJ, et al: Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J Appl Physiol 74:2566-2573, 1993 13. Felbinger TW, Reuter DA, Eltzschig HK, et al: Comparison of pulmonary arterial thermodilution and arterial pulse contour analysis: Evaluation of a new algorithm. J Clin Anesth 14:296-301, 2002 14. Godje O, Peyerl M, Seebauer T, et al: Reproducibility of double indicator dilution measurements of intrathoracic blood volume compartments, extravascular lung water, and liver function. Chest 113: 1070-1077, 1998 15. Pauli C, Fakler U, Genz T, et al: Cardiac output determination in children: Equivalence of the transpulmonary thermodilution method to the direct Fick principle. Intensive Care Med 28:947-952, 2002 16. Sakka SG, Reinhart K, Meier-Hellmann A: Comparison of pulmonary artery and arterial thermodilution cardiac output in critically ill patients. Intensive Care Med 25:843-846, 1999 17. Manecke GR: Edwards FloTrac sensor and Vigileo monitor: Easy, accurate, reliable cardiac output assessment using the arterial pulse wave. Expert Rev Med Devices 2:523-527, 1005 18. Langewouters GJ, Wesseling KH, Goedhard WJ: The pressure dependent dynamic elasticity of 35 thoracic and 16 abdominal human aortas in vitro described by a five component model. J Biomech 18:613-620, 1985 19. Manecke GR Jr, Auger WR: Cardiac output determination from the arterial pressure wave: Clinical testing of a novel algorithm that does not require calibration. J Cardiothorac Vasc Anesth 21:3-7, 2007 20. McGee W HJ, Janvier G: Validation of a continuous cardiac output measurement using arterial pressure waveforms. Crit Care 9:P62, 2005

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21. Bogert LW, van Lieshout JJ: Noninvasive pulsatile arterial pressure and stroke volume changes from the human finger. Exp Physiol 90:437-446, 2005 22. Langewouters GJ, Wesseling KH, Goedhard WJ: The static elastic properties of 45 human thoracic and 20 abdominal aortas in vitro and the parameters of a new model. J Biomech 17:425-435, 1984 23. Remmen JJ, Aengevaeren WR, Verheugt FW, et al: Finapres arterial pulsewave analysis with Modelflow is not a reliable noninvasive method for assessment of cardiac output. Clin Sci (Lond) 103:143-149, 2002 24. Jansen JR, Schreuder JJ, Mulier JP, et al: A comparison of cardiac output derived from the arterial pressure wave against thermodilution in cardiac surgery patients. Br J Anaesth 87:212-222, 2001 25. Azabji Kenfack M, Lador F, Licker M, et al: Cardiac output by Modelflow method from intra-arterial and fingertip pulse pressure profiles. Clin Sci (Lond) 106:365-369, 2004 26. Tam E, Azabji Kenfack M, Cautero M, et al: Correction of cardiac output obtained by Modelflow from finger pulse pressure profiles with a respiratory method in humans. Clin Sci (Lond) 106:371376, 2004. 27. Settels J: Finometer: Preliminary Description. 2001. Available at: http://www.finapres.com/files/articledownloads/full-settels-2001.pdf. Accessed April 15, 2008 28. Romano SM, Pistolesi M: Assessment of cardiac output from systemic arterial pressure in humans. Crit Care Med 30:1834-1841, 2002 29. Giomarelli P, Biagioli B, Scolletta S: Cardiac output monitoring by pressure recording analytical method in cardiac surgery. Eur J Cardiothorac Surg 26:515-520, 2004 30. Romano SM, Scolletta S, Olivotto I, et al: Systemic arterial waveform analysis and assessment of blood flow during extracorporeal circulation. Perfusion 21:109-116, 2006 31. Ishihara H, Okawa H, Tanabe K, et al: A new noninvasive continuous cardiac output trend solely utilizing routine cardiovascular monitors. J Clin Monit Comput 18:313-320, 2004