Ensuring adequate oxygen (O2) delivery, hence tissue oxygenation and utilization, in the critically ill is one of the main tasks in maintaining life support. The importance of tissue O2 utilization is highlighted in the Consensus definition of ‘shock’ published by the Task Force of the European Society of Intensive Care Medicine: ‘…life-threatening, generalized form of acute circulatory failure associated with inadequate oxygen utilization by the cells’ . It is futile to maintain high arterial O2 content if the O2 cannot be delivered to the tissues. This delivery of O2 is contingent on cardiac output (CO):
As such, CO is often used as a surrogate of O2 delivery and is an essential part of hemodynamic monitoring in critically ill patients.
Bedside CO measurements serve two main purposes: for differentiating the types of circulatory shock and for assisting fluid management . In fact, examination of stroke volume (SV) or left ventricular ejection fraction (LVEF) provides some qualitative insights about the ventriculoarterial coupling .
Many bedside CO measurement devices have been developed over the last quarter of a century. There has been a clear direction of development towards minimally or noninvasive methods . The ability to continuously monitor CO noninvasively is another important feature that has developed in the last decades [4,5]. This review summarizes the common utility of CO monitoring and the methods used for bedside monitoring. A number of excellent articles on CO monitoring are already available [3,6,7]; this review aims to present some recent findings and to supplement these articles using a slightly different approach.
PURPOSES OF CARDIAC OUTPUT MEASUREMENT
Differential diagnosis of circulatory shock
SV is determined by the interaction between LV contractility and afterload offered by the arterial system, that is, the arterial system must be able to accommodate the SV ejected by the LV. This phenomenon is known as ventriculoarterial (VA) coupling and can be quantified by LV contractility to afterload ratio, or the end-systolic elastance (Ees) to arterial elastance (Ea) ratio [8,9]. Physiologically, Ees/Ea ratio is maintain at a value, normally between 1 and 2, where the stroke work and cardiac metabolic efficiency are maximized [8,10,11]. Hence, SV (and LVEF) is determined by Ees/Ea ratio. Different types of hemodynamic derangements result in different Ees/Ea ratios, hence SV. Some decreases Ees (e.g. heart failure), some decreases Ea (e.g. vasoplegia in septic shock), and some may affect both but to different extent [12,13]. The characteristic difference in SV in these situations can be explained by examining the Ees–Ea interaction in the pressure–volume relationship graphs, and also explains why measuring SV or CO is useful (Fig. 1). For example, the different types of circulatory shock, namely cardiogenic, hypovolemic, obstructive, and distributive, can be differentiated by measuring the CO (= SV × heart rate) . In general, cardiogenic, hypovolemic and obstructive shock are characterized by low CO, implying inadequate O2 delivery. On the other hand, CO is usually high in distributive shock (e.g. septic shock), unless also accompanied by myocardial depression or cardiac dysfunction then the CO will be low (e.g. mixed septic and cardiogenic shock). Figure 1 shows that although some circulatory shocks are characterized by low SV (hence CO), they exhibit different VA coupling properties.
After diagnosing the type of shock, O2 administration (e.g. mechanical ventilation) is usually followed by fluid administration to improve tissue perfusion and oxygenation. Patients with circulatory shock usually receive some benefits from fluid administration, but the challenge is to decide when to stop giving fluid and this decision is achieved by examining if the patient is fluid responsive or not [15,16▪▪]. Although various methods are available, the objective is to ensure the cardiac function is not operating on the preload-independent zone (i.e. the plateau portion of the Frank–Starling curve) when administering fluid (see accompanying article on Optimizing Fluid Therapy in Shock in this issue by Paul Marik). In principle, the procedure includes varying the preload of a patient (e.g. by mini volume administration, passive leg raising manoeuvre or respiratory-induced change in preload) while his/her CO or SV is monitored for a significant change [17,18].
MEASURING CARDIAC OUTPUT
There are different types of CO measuring devices available in the market, and can be divided into two broad types based on the method used: one estimates CO using physical principles, and the other derived from mathematical models (Fig. 2).
Estimation of cardiac output using physical principles
Using simple physical principles, such as conservation of mass or energy, these devices offer more reliable and accurate measurements of CO. Mathematical conversion from arterial pressure to flow are not required. Three main measurements methods are used under this category: Fick's principle, dilution method and Doppler ultrasound. While these methods yield more reliable results, most are not suitable for continuous CO monitoring.
The original Fick's method is based on the premise that the rate of O2 consumption (= O2 uptake) per minute
equals to the product of CO and arteriovenous O2 content difference (CaO2–CvO2):
While the principle appears simple, the measurement procedure is cumbersome and involves the use of calorimeter, and venous and arterial blood sampling. This method is invasive and seldom used nowadays.
Partial CO2 re-breathing method
The partial CO2 re-breathing method applies the Fick's principle to CO2 elimination. The re-breathing technique is used in place of invasive blood sampling in estimating arterial and mixed venous CO2 contents . Although the method is easy to use, it can only be used in mechanically ventilated patients free from severe hypercapnia, increased intracranial pressure or pulmonary hypertension. A recent meta-analysis reported a wide range of bias and percentage error using this method [20▪▪].
Based on the principle of conservation of energy and mass, the dilution method injects a known amount of indicator into the blood stream (e.g. cold saline or lithium) and measures the total change in the indicator's concentration (or temperature) in the blood over a period of time . If the period of time (t) monitored is complete, the total change in concentration (or temperature), as measured by area under the curve (AUC), will equal to the total amount of indicator injected (m) diluted by the volume of blood available in that period of time (V):
Since V = CO × t, hence
At present, two main indicators are used for dilution method: thermoindicator (e.g. cold fluid) and lithium. Pulmonary artery catheter (PAC) uses intermittent thermodilution method where cold fluid is used as indicator. This method is regarded as the standard for CO measurement. Continuous CO monitoring is also possible by including a heating filament in the catheter. The temperature change is detected downstream by a thermistor . While PAC method injects cold fluid near the right atrium entrance and the dilution curve is detected in the pulmonary artery, a similar method, transpulmonary thermodilution, detects the dilution in the femoral artery making it less accurate due to loss of indicator in the lung [see also ‘Transpulmonary thermodilution techniques in the hemodynamically unstable patients’ by Xavier Monnet (273–279)]. The invasiveness nature of these methods is probably the main drawback.
Transpulmonary lithium dilution uses a small dose of lithium chloride as indicator. The bolus is injected intravenously, and the dilution curve is detected by a lithium sensor in a peripheral arterial line. In contrast to thermodilution, lithium dilution needs to take packed cell volume into account because lithium is only diluted in the plasma and not in the blood cells, hence blood sampling is required .
The accuracy of dilution method depends on whether or not enough time is allowed to determine the complete dilution curve, complete mixing of indicator with the blood is allowed and the measurement of the change in temperature or indicator concentration is sensitive and accurate enough. Presence of significant tricuspid regurgitation distorts the dilution curve, and results in underestimation of CO .
Doppler ultrasound is a noninvasive method of CO determination. The principle involves measuring the instantaneous velocities of the LV outflow tract (LVOT) or aorta by Doppler ultrasound. SV is calculated by multiplying the summation of velocities over one heartbeat [known as velocity time integral (VTI)] by the cross-sectional area (CSA):
CO is then obtained by multiplying SV by heart rate. Accuracy relies on proper alignment of ultrasound beam with blood flow and precise measurement of LVOT diameter. Aorta is not normally used in proper CO measurement because of the change in aortic size during the cardiac cycle.
Two Doppler ultrasound methods are available: oesophageal Doppler monitoring (EDM) and transthoracic echocardiography (TTE). EDM is a minimally invasive method requiring the insertion of an oesophageal probe. It is not a full ultrasound device and is only dedicated to measure CO from the descending thoracic aorta. This method is limited by the fact that the aortic diameter is not measured but estimated from patient's age and height/weight. Even if the estimation is accurate, it is unable to tract the significant CSA changes over the course of a heartbeat and relate it to the flow. Furthermore, EDM assumes the descending aorta receives 30% of the total CO which may not be true. Angle of insonation is also a problem leading to underestimation of CO . On comparison, TTE provides 2D imaging and colour flow mapping allowing proper alignment of ultrasound beam and accurate measurement of LVOT diameter, hence a much more reliable result. It also provides other important information such as ventricular size and function as well as ejection fraction, which are valuable in differentiating cardiogenic shock from other circulatory shock. TTE measures CO directly from the LVOT, and makes no assumption of distribution of blood. The main disadvantages of TTE are the requirements of skilful operator and expensive ultrasound machines. While EDM provides continuous monitoring, TTE only performs point estimates of CO.
Prediction of cardiac output from modelling
These devices do not estimate blood flow directly, but instead they predict CO from mathematical modelling. As with all prediction modelling, the accuracy and applicability depend on the population used for model development and the assumptions made. At present, two types of devices are available: one that predict CO or SV from arterial pressure waveform, and the other from thoracic electrical properties. As these devices are either minimally invasive or noninvasive, they are the main choice for continuous CO monitoring.
Arterial waveform analysis
There are different types of arterial waveform analysis (also known as pulse contour) devices, each using a different proprietary algorithm (mathematical model). Most of these algorithms are based on Otto Frank's work on the shape of arterial pulse, and converting arterial pulse (size and shape) into flow (i.e. SV or CO) [26,27]. These models usually predict individual's arterial compliance and systemic vascular resistance from biometric data such as age, gender, weight and height, which are then combined with arterial pressure information to yield the SV [28,29]. Understandably, the effects of vasopressors and inotropes were often not considered in the model, or at least in the original model. Table 1 shows some of the different mathematical models used by these devices [29–31]. Note that they all predict SV from arterial pressure information. A few studies compared the accuracy of these algorithms with thermodilution and EDM, and the overall results were disappointing [31,32].
Since these devices predict CO from mathematical models of which the prediction accuracy is only as good as the original population were based on, they will not be as accurate and reproducible as methods that measure flow and concentration directly. To overcome this issue, some devices requires an initial CO calibration by either transpulmonary thermodilution (e.g. PiCCOplus and EV1000/VolumeView) or lithium dilution (e.g. LiDCOplus) before the start of monitoring . That said, the alteration of cardiovascular properties, such as by changes in physiological states or treatment effects, may render the model invalid. A meta-analysis conducted in 2016 also showed that the percentage errors of these devices were higher than acceptable level [20▪▪]. However, growing knowledge of the cardiovascular system, accumulation of data beyond the original testing population and understanding of drug actions lead to refinement of these models and constantly updating of the algorithms (software versions). While this may improve the model accuracy, but it makes summarizing the accuracy (bias) and precision of these devices difficult as the reports might be outdated quickly.
Pulse wave transit time
Instead of analysing arterial waveform, pulse wave transit time device, sometimes known as estimated continuous CO (esCCO), assumes SV is proportion to the arterial pulse transit time from ECG R-wave to the rise point of pulse oximetry at the fingertip . Pulse wave transit time depends on arterial elasticity and resistance. A preliminary study showed that esCCO correlated with TTE CO, and had acceptable accuracy and percentage error . However, subsequent studies casted doubt on its reliability and tracking ability [35,36].
Thoracic bioelectrical properties
These devices measure the change in thoracic electrical bioimpedance (TEB or Z) as a result of change in intrathoracic blood volume. Electrodes are applied at the base of the neck (thoracic inlet) and the costal margins (thoracic outlet). A high-frequency electrical current of known amplitude and frequency is applied across the thorax. The changes in voltage are measured throughout the cardiac cycle, and the corresponding change in Z is calculated. Z changes as the intrathoracic volume changes during systole and diastole. Since the instantaneous change in Z (i.e. dZ/dt) is proportional to the change in aortic blood flow, SV can then be calculated from ECG ejection time (T) and the distance between the inlet and outlet electrodes (L) :
TEB is sensitive to electrical interference, electrode positions (L above), and patient movement. Age, presence of pulmonary oedema, pleural or pericardial effusion, mechanical ventilation and arrhythmias also affect its accuracy [38,39]. The percentage error and bias in critically ill patients when compared to thermodilution method was high [20▪▪,38,39].
These devices use a similar procedure as TEB method, but instead of detecting voltage change, the change in relative phase shift (ϕ) between the input electrodes and the receiving electrodes are used. As aortic flow rate is proportional to the rate of change of ϕ (dϕ/dt), SV is calculated from the maximal dϕ/dt and ejection time (T) :
Bioreactance method is less sensitive to body size and movement, and electrode positions . However, the measurements were affected by pulmonary oedema and pleural fluid . To date, the accuracy of bioreactance method remains controversial [41–43].
CO (or SV) measurement is an important component in hemodynamic monitoring. It assists differential diagnosis of circulatory shock and determination of fluid responsiveness. There are a number of CO measuring and monitoring devices, some of which uses simple physical principles and others use mathematical modelling. While the former offer better accuracy, the latter offer trending ability. PAC thermodilution is still the reference standard for CO measurement, but routine uses is limited by its invasiveness. Instead, TTE offers an alternative to thermodilution by virtue its accuracy and noninvasiveness.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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- ▪ of special interest
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