Cardiac output

Cardiac output is the volume of blood being pumped by the heart, in particular a ventricle in a minute. It is equal to the heart rate multiplied by the stroke volume.

Therefore, if there are 70 beats per minute, and 70 ml blood is ejected with each beat of the heart, the cardiac output is 4900 ml/minute. This value is typical for an average adult at rest, although cardiac output may reach up to 30 liters/minute during extreme exercise.

When cardiac output increases in a healthy but untrained individual, most of the increase can be attributed to increase in heart rate. Change of posture, increased sympathetic nervous system activity, and decreased parasympathetic nervous system activity can also increase cardiac output. Heart rate can vary by a factor of approximately 3, between 60 and 180 beats per minute, whilst stroke volume can vary between 70 and 120 ml, a factor of only 1.7.

A parameter that is related to stroke volume is Ejection Fraction (EF). EF is the fraction of blood ejected by the Left Ventricle (LV) during the contraction phase of the cardiac cycle (known as Systole). At the start of Systole, the LV is filled with blood to the capacity known as End Diastolic Volume. During Systole, the LV contracts and ejects blood until it reaches its minimum capacity known as End Systolic Volume.

Stroke Volume (SV) = EDV – ESV

Ejection Fraction (EF) = (SV / EDV) × 100%

Cardiac Output (CO) = SV × HR'''

Cardiac Index (CI) = CO / BSA = SV × HR/BSA


 * HR is Heart Rate, expressed as BPM (Beats Per Minute)
 * BSA is Body Surface Area in square metres.

Measuring Cardiac Output
There are many invasive and several non-invasive methods for measuring cardiac output in mammals.

A non-invasive method, often used in teaching students of physiology, reasons as follows:
 * The pressure in the heart rises as blood is forced into the aorta
 * The more stretched the aorta, the greater the pulse pressure
 * In healthy young subjects, each additional 2 ml of blood results in a 1 mmHg rise in pressure
 * Therefore:
 * Stroke Volume = 2 ml × Pulse Pressure
 * Cardiac Output = 2 ml × Pulse Pressure × Heart Rate

Magnetic Resonance Imaging
Velocity encoded phase contrast Magnetic Resonance Imaging (MRI) is the most accurate technique for measuring flow in large vessels in mammals. MRI flow measurements have been shown to be highly accurate compared to measurements with a beaker and timer, and less variable than both the Fick principle and thermodilution.

Velocity encoded MRI is based on detection of changes in the phase of proton precession. These changes are proportional to the velocity of the movement of those protons through a magnetic field with a known gradient. When using velocity encoded MRI, the result of the MRI scan is two sets of images for each time point in the cardiac cycle. One is an anatomical image and the other is an image where the signal intensity in each pixel is directly proportional to the through-plane velocity. The average velocity in a vessel, i.e. the aorta or the pulmonary artery, is hence quantified by measuring the average signal intensity of the pixels in the cross section of the vessel, and then multiplying by a known constant. The flow is calculated by multiplying the mean velocity by the cross-sectional area of the vessel. This flow data can be used to graph flow versus time. The area under the flow versus time curve for one cardiac cycle is the stroke volume. The length of the cardiac cycle is known and determines heart rate, and thereby cardiac output can be calculated as the product of stroke volume and heart rate.

The Fick Principle
Fick principle involves measuring:
 * VO2 consumption per minute using a spirometer (with the subject re-breathing air) and a CO2 absorber
 * the oxygen content of blood taken from the pulmonary artery (representing mixed venous blood)
 * the oxygen content of blood from a cannula in a peripheral artery (representing arterial blood)

From these values, we know that:
 * $$VO_2 = (CO \times\ C_A) - (CO \times\ C_V)$$

where CO = Cardiac Output, CA = Oxygen concentration of arterial blood and CV = Oxygen concentration of venous blood.

This allows us to say
 * $$CO = \frac{VO_2}{C_A - C_V}*100$$

and therefore calculate cardiac output.

Dilution methods
This method measures how fast flowing blood can dilute an indicator substance introduced to the circulatory system, usually using a pulmonary artery catheter. Early methods used a dye, the cardiac output being inversely proportional to the concentration of dye sampled downstream. More specifically, the cardiac output is equal to the quantity of indicator dye injected divided by the area under the dilution curve measured downstream (the Stewart-Hamilton equation):


 * $$Cardiac\ output = \frac{Quantity\ of\ Indicator}{\int_0^\infty Concentration\ of\ Indicator\cdot {dt}}$$

The trapezoid rule is often used as an approximation of this integral. A more modern technique is to use cold saline as the indicator, and then measure the change in temperature downstream. Cardiac output can be affected by the phase of respiration, especially under mechanical ventilation, and should therefore be measured at a defined phase of the respiratory cycle (typically end-expiratory).

Doppler method
This technique uses ultrasound and the Doppler effect to measure cardiac output. The blood velocity through the aorta cause a 'Doppler shift' in the frequency of the returning ultrasound waves. Echocardiographic measurement of the aortic root cross-sectional area (or, alternatively, the descending aorta area) multiplied by the measured velocity time integral of flow through that area and heart rate, yields the cardiac output.

Pulmonary Artery Thermodilution (Trans-right-heart Thermodilution)
The pulmonary artery catheter (PAC) also known as the Swan-Ganz thermodilution catheter provides right heart blood pressures. Using the PAC thermodilution cardiac output can be measured. Modern catheters are fitted with a distal heated filament, which allows automatic thermodilution measurement via heating the blood and measuring the resultant thermodilution trace. This provides near continuous cardiac output monitoring. The PAC is used in assessment of hemodynamic status and direct intracardiac and pulmonary artery pressures. The distal (pulmonary artery) port allows sampling of mixed venous blood for the assessment of oxygen transport and the calculation of derived parameters such as oxygen consumption, oxygen utilization coefficient, and intrapulmonary shunt fraction.

The PAC is balloon tipped which can be inflated to occlude the pulmonary artery, the subsequence back pressure is a reflection of the left atrial filling pressure and until recently was considered a good indicator of preload.

The pulmonary artery wedge pressure (PAWP) has been superseded by more reliable techniques such as intrathoracic blood volume or stroke volume variation as indicators of volume status. The PAC also allows sampling of mixed venous blood, the oxygen content of which can be used to indicate the adequacy of overall oxygen delivery. The PAC has fallen out of common use as clinicians favour less invasive, less hazardous technologies for monitoring haemodynamic status. Considerable controversy exists over whether the PAC increases mortality; recent studies suggest it neither increases nor improves mortality. Complications such as cardiac tamponade, pulmonary artery rupture and air emboli are a danger.

PulseCO and PiCCO Technology
PiCCO (PULSION Medical Systems AG, Munich, Germany) and PulseCO (LiDCO Ltd, London, England) generate continuous cardiac output by analysis of the arterial blood pressure waveform. In both cases, an independent technique is required to provide initial calibration of the continuous cardiac output analysis, as arterial waveform analysis cannot account for unmeasured variables such as compliance of the vascular tree.

In the case of PiCCO, transpulmonary thermodilution is used as the independent technique. This uses the Stewart-Hamilton principle outlined above, but measured from central venous line to a central (i.e. femoral or axillary) arterial line. The cardiac output derived from this cold-saline thermodilution is used to calibrate the arterial pulse contour analysis, which can then provide continuous cardiac output monitoring. The PiCCO algorithm is dependent on blood pressure waveform morphology (i.e. mathematical analysis of the pulse contour waveform) and calculates continuous cardiac output as described by Wesseling and co-workers. Transpulmonary thermodilution spans right heart, pulmonary circulation and left heart; this allows further mathematical analysis of the thermodilution curve, giving measurements of cardiac filling volumes (GEDV), intrathoracic blood volume, and extravascular lung water.

In the case of LiDCO, the independent calibration technique is lithium dilution, again using the Stewart-Hamilton principle. Lithium dilution has the advantage of being usable from a peripheral vein to a peripheral arterial line; however, it does not provide information on cardiac filling volumes and extravascular lung water. Dilution measurements cannot be performed too frequently, and can be subject to error in the presence of certain muscle relaxants. The PulseCO algorithm used by LiDCO is based on pulse power derivation and is not dependent on waveform morphology.

FloTrac technology
A more recent development is the FloTrac system which can derive cardiac output from the arterial waveform without the need for an independent method of calibration. Hence continuous cardiac output can be measured directly from a conventional arterial line. This method has yet to be extensively evaluated, but early studies suggest that it is accurate. Another similar system that uses the arterial pulse is the pressure recording analytical method (PRAM). Neither the FloTrac nor the PRAM require external calibration.

Impedance cardiography
Impedance cardiography (ICG) is an advanced technique which was developed by NASA. It calculates cardiac output based on the measurement of changes in impedance in the chest over the cardiac cycle. This technique has progressed clinically (often called BioZ, i.e. biologic impedance, as promoted by the leading manufacturer in the US) and allows low cost, non-invasive estimations of cardiac output and total peripheral resistance, using only 4 paired skin electrodes, with minimal removal of clothing in physician offices having the needed equipment.

Equations
By simplifying D'arcy's Law, we get the equation that
 * $$ Flow = \frac{Pressure} {Resistance}$$

When applied to the circulatory system, we get:
 * $$ Cardiac\ Output = \frac{ABP - RAP}{TPR}$$

Where ABP = Aortic (or Arterial) Blood Pressure, RAP = Right Atrial Pressure and TPR = Total Peripheral Resistance.

However, as ABP>>RAP, and RAP is approximately 0, this can be simplified to:
 * $$Cardiac\ Output \approx \frac{Aortic\ Blood\ Pressure}{Total\ Peripheral\ Resistance}$$

Physiologists will often re-arrange this equation, making ABP the subject, to study the body's responses.

As has already been stated, Cardiac Output is also the product of the heart rate and the stroke volume, which allows us to say:


 * $$Heart\ Rate \times Stroke\ Volume \approx \frac{ABP}{TPR}$$