Haemodynamic Monitoring Theory and Practice

Principles of Measurement Introduction to the PiCCO-Technology – Function Principles of Measurement PiCCO Technology is a combination of transpulmonary thermodilution and pulse contour analysis CVC Lungs Pulmonary Circulation central venous bolus injection PiCCO technology is a complete haemodynamic monitoring system based on the transpulmonary thermodilution technique. An indicator (cold) is injected into the circulation and the course of its concentration downstream is recorded. In the case of PiCCO technology, this means central venous injection of a cold bolus and detection of the temperature course in a peripheral large artery (femoral, axillary, brachial) through a special thermodilution catheter. The second component of PiCCO technology is pulse contour analysis, which is calibrated from the results of the thermodilution measurement and delivers continuous haemodynamic parameters in contrast to intermittent thermodilution. Right Heart Left Heart PULSIOCATH arterial thermodilution catheter PULSIOCATH PULSIOCATH Body Circulation

Principles of Measurement Introduction to the PiCCO-Technology – Function Principles of Measurement After central venous injection the cold bolus sequentially passes through the various intrathoracic compartments Bolus injection RA RV LA LV PBV EVLW concentration changes over time (Thermodilution curve) This is a diagram of the pathway followed by the indicator following injection: following central venous injection, first through the right heart (atrium and ventricle), then through the lung, then through the left heart (atrium and ventricle) and the aorta as far as the detection site (location of the thermodilution catheter). The individual cardiac chambers and the lung with the extravascular lung water are thus mixing chambers in which the cold bolus is distributed. Right heart Lungs Left heart The temperature change over time is registered by a sensor at the tip of the arterial catheter

Intrathoracic Thermal Volume (ITTV) Pulmonary Thermal Volume (PTV) Introduction to the PiCCO-Technology – Function Intrathoracic Compartments (mixing chambers) Intrathoracic Thermal Volume (ITTV) Pulmonary Thermal Volume (PTV) RA RV LA LV PBV EVLW The totality of all mixing chambers, that is, all four cardiac chambers, the pulmonary circulation and the extravascular lung water forms the total intrathoracic thermal volume. This designates the total intrathoracic distribution volume for cold. The largest single mixing chamber in this system is the pulmonary thermal volume, which consists of the blood volume of the pulmonary circulation and the extravascular lung water. Largest single mixing chamber Total of mixing chambers

Haemodynamic Monitoring E. Introduction to PiCCO Technology Principles of function Thermodilution Pulse contour analysis Contractility parameters Afterload parameters Extravascular Lung Water Pulmonary Permeability

(Tb - Ti) x Vi x K COTD a = D Tb x dt Introduction to the PiCCO-Technology – Thermodilution Calculation of the Cardiac Output The CO is calculated by analysis of the thermodilution curve using the modified Stewart-Hamilton algorithm Tb Injection t (Tb - Ti) x Vi x K Various volume parameters can be calculated from the thermodilution curve, which is recorded via the thermodilution catheter (PiCCO catheter). One of the main parameters of thermodilution measurement is the cardiac output, which is calculated using the modified Stewart-Hamilton algorithm from the area under the thermodilution curve. The Stewart Hamilton algorithm is not specific for PiCCO but is already relatively old and well validated. It is also the basis, e.g., for measuring CO by means of pulmonary arterial thermodilution with the pulmonary artery catheter. COTD a = D Tb x dt ∫ Tb = Blood temperature Ti = Injectate temperature Vi = Injectate volume ∫ ∆ Tb . dt = Area under the thermodilution curve K = Correction constant, made up of specific weight and specific heat of blood and injectate

Thermodilution curves Introduction to the PiCCO-Technology – Thermodilution Thermodilution curves The area under the thermodilution curve is inversely proportional to the CO. Temperature 36,5 Normal CO: 5.5l/min 37 Temperature Time 36,5 low CO: 1.9l/min Important conclusions about the level of the CO can be drawn from the shape of the thermodilution curve. The area under the thermodilution curve is inversely proportional to the CO, i.e. when the CO is high, the area is small and vice versa. When the CO is high, the cold bolus arrives sooner at the thermistor so the curve is shifted to the left compared to the normal and reduced CO. The reverse applies for a reduced CO, so the curve is shifted to the right. 37 Temperature Time 36,5 High CO: 19l/min 37 5 10 Time

Transpulmonary TD (PiCCO) Pulmonary Artery TD (PAC) Introduction to the PiCCO –Technology – Thermodilution Transpulmonary vs. Pulmonary Artery Thermodilution Transpulmonary TD (PiCCO) Pulmonary Artery TD (PAC) Aorta PA Pulmonary Circulation Lungs LA central venous bolus injection RA LV PULSIOCATH arterial thermo-dilution catheter RV The principle of thermodilution with the PiCCO technology is identical to the pulmonary artery catheter (PAC), However, while the temperature bolus is detected in the pulmonary artery with the PAC, this takes place in a large peripheral artery (femoral, axillary or brachial) with the PiCCO system after passage through the heart and lungs. With both methods, not the entire injected indicator flows past the thermistor since this is in a branch of the pulmonary artery. This has no influence on the validity of the result with either measurement method as the detected amount of the indicator is not relevant but rather the difference in temperature over time. Pictorial comparison: a stone falls into smooth water and generates a wave that spreads in all directions. The height of the wave can be measured at any location but the same result will always be obtained. Right Heart Left heart Body Circulation In both procedures only part of the injected indicator passes the thermistor. Nonetheless the determination of CO is correct, as it is not the amount of the detected indicator but the difference in temperature over time that is relevant!

Extended analysis of the thermodilution curve Introduction to the PiCCO-Technology – Thermodilution Extended analysis of the thermodilution curve From the characteristics of the thermodilution curve it is possible to determine certain time parameters Tb Injection Recirculation In Tb e-1 However, not only the CO but other volume parameters can be calculated from the thermodilution curve. The curve undergoes extended analysis and two time parameters are determined: MTt Mean transit time, time from injection to the point at which the thermodilution curve has fallen to 75% of its maximum. This corresponds to the average time that the indicator requires from injection to detection. DST: Downslope time, time in which the thermodilution curve falls from 75% of its maximum to 25% of its maximum. This period represents the mixing behaviour of the indicator in the largest single mixing chamber. The theoretical principles of indicator dilution are very complex but already long familiar (Newman 1951) and validated. MTt DSt t MTt: Mean Transit time the mean time required for the indicator to reach the detection point DSt: Down Slope time the exponential downslope time of the thermodilution curve Tb = blood temperature; lnTb = logarithmic blood temperature; t = time

Intrathoracic Thermal Volume Pulmonary Thermal Volume Introduction to the PiCCO-Technology – Thermodilution Calculation of ITTV and PTV By using the time parameters from the thermodilution curve and the CO ITTV and PTV can be calculated Tb Injection Recirculation In Tb e-1 If the cardiac output is multiplied by the mean transit time, the intrathoracic thermal volume (ITTV) is obtained. This is the total distribution volume for cold in the thorax. The volume of the biggest single mixing chamber for cold in the thorax, the pulmonary thermal volume (PTV), is obtained by multiplying the CO by the downslope time. MTt DSt t Intrathoracic Thermal Volume ITTV = MTt x CO Pulmonary Thermal Volume PTV = Dst x CO

Intrathoracic Thermal Volume (ITTV) Pulmonary Thermal Volume (PTV) Einführung in die PiCCO-Technologie – Thermodilution Calculation of ITTV and PTV Intrathoracic Thermal Volume (ITTV) Pulmonary Thermal Volume (PTV) RA RV LA LV PBV EVLW Repeat of the diagram of the individual compartments. The ITTV refers to the sum of all the mixing chambers in the thorax, that is, the total intrathoracic distribution volume for cold. The PTV represents the largest single mixing chamber in the thorax, the pulmonary theramal volume, which consists of the blood volume of the pulmonary circulation (pulmonary blood volume, PBV) and the extravascular lung water (EVLW). PTV = Dst x CO ITTV = MTt x CO

Global End-diastolic Volume (GEDV) Introduction to the PiCCO –Technology – Thermodilution Volumetric preload parameters – GEDV Global End-diastolic Volume (GEDV) ITTV PTV RA RV LA LV PBV EVLW If the pulmonary thermal volume is now subtracted from the intrathoracic thermal volume, the total blood volume in all 4 cardiac chambers is obtained. This is also called the global end-diastolic volume. This is a volumetric parameter that gives information about the filling condition of the heart and thus about cardiac preload. GEDV GEDV is the difference between intrathoracic and pulmonary thermal volumes

Intrathoracic Blood Volume (ITBV) Introduction to the PiCCO –Technology – Thermodilution Volumetric preload parameters – ITBV Intrathoracic Blood Volume (ITBV) GEDV RA RV LA LV PBV EVLW PBV If the blood volume present in the pulmonary circulation (pulmonary blood volume, PBV) is now added to the global end-diastolic volume, the intrathoracic blood volume is obtained. This thus represents the total blood volume present in the heart and pulmonary circulation. ITBV ITBV is the total of the Global End-Diastolic Volume and the blood volume in the pulmonary vessels (PBV)

ITBV is calculated from the GEDV by the PiCCO Technology Introduction to the PiCCO-Technology – Thermodilution Volumetric preload parameters – ITBV ITBV is calculated from the GEDV by the PiCCO Technology Intrathoracic Blood Volume (ITBV) ITBVTD (ml) 1000 2000 3000 The intrathoracic blood volume can be measured either directly by double indicator dilution or – as with PiCCO technology – calculated reliably from the GEDV. The ITBV is usually 25% higher than the GEDV. ITBV = 1.25 * GEDV – 28.4 [ml] GEDV (ml) GEDV vs. ITBV in 57 Intensive Care Patients Sakka et al, Intensive Care Med 26: 180-187, 2000

Intrathoracic Thermal Volume (ITTV) Pulmonary Thermal Volume (PTV) Introduction to the PiCCO-Technology – Function Intrathoracic Compartments (mixing chambers) Intrathoracic Thermal Volume (ITTV) Pulmonary Thermal Volume (PTV) RA RV LA LV PBV EVLW The totality of all mixing chambers, that is, all four cardiac chambers, the pulmonary circulation and the extravascular lung water forms the total intrathoracic thermal volume. This designates the total intrathoracic distribution volume for cold. The largest single mixing chamber in this system is the pulmonary thermal volume, which consists of the blood volume of the pulmonary circulation and the extravascular lung water. Largest single mixing chamber Total of mixing chambers

ITTV – ITBV = EVLW Calculation of Extravascular Lung Water (EVLW) Introduction to the PiCCO –Technology – Extravascular Lung Water Calculation of Extravascular Lung Water (EVLW) ITTV – ITBV = EVLW To detect and quantify pulmonary oedema, PiCCO technology measures the extravascular lung water, which represents the water content of the lungs outside the blood vessels. It corresponds to the difference between the total intrathoracic distribution volume for cold (ITTV) and the blood volume in the thorax (ITBV). The Extravascular Lung Water is the difference between the intrathoracic thermal volume and the intrathoracic blood volume. It represents the amount of water in the lungs outside the blood vessels.

Validation of Extravascular Lung Water Introduction to the PiCCO –Technology – Extravascular Lung Water Validation of Extravascular Lung Water EVLW from the PiCCO technology has been shown to have a good correlation with the measurement of extravascular lung water via the gravimetry and dye dilution reference methods Gravimetry Dye dilution ELWI by PiCCO ELWIST (ml/kg) Y = 1.03x + 2.49 40 25 30 20 n = 209 r = 0.96 15 PiCCO measurement of the extravascular lung water was validated against the reference methods, gravimetry (in sheep) and dye dilution. Correlation excellent for clinical purposes was demonstrated between the much simpler PiCCO thermodilution measurement and the reference methods. 20 10 10 5 R = 0,97 P < 0,001 10 20 30 5 10 15 20 25 ELWI by gravimetry ELWITD (ml/kg) Katzenelson et al,Crit Care Med 32 (7), 2004 Sakka et al, Intensive Care Med 26: 180-187, 2000

Haemodynamic Monitoring E. Introduction to PiCCO Technology Principles of function Thermodilution Pulse contour analysis Contractility parameters Afterload parameters Extravascular Lung Water Pulmonary Permeability

Calibration of the Pulse Contour Analysis Introduction to the PiCCO-Technology – Pulse contour analysis Calibration of the Pulse Contour Analysis The pulse contour analysis is calibrated through the transpulmonary thermodilution and is a beat to beat real time analysis of the arterial pressure curve Transpulmonary Thermodilution Pulse Contour Analysis Injection The continuous pulse contour analysis is calibrated by transpulmonary thermodilution measurement. The stroke volume obtained with thermodilution is placed in relation to the area under the systolic part of the arterial pulse curve. Using this calibration, the cardiac output can then be determined continuously from the arterial pressure curve (pulse contour). COTPD = SVTD HR T = blood temperature t = time P = blood pressure

( Parameters of Pulse Contour Analysis   P(t) dP PCCO = cal • HR • Introduction to the PiCCO-Technology – Pulse contour analysis Parameters of Pulse Contour Analysis Cardiac Output   Area under the pressure curve P(t) Shape of the pressure curve dP Patient- specific calibration factor (determined by thermodilution) Besides the area under the pressure curve and other factors, calculation of the continuous PiCCO pulse contour cardiac output also involves the aortic compliance measured by thermodilution, which represents an important advantage compared to systems that cannot be calibrated. PCCO = cal • HR • ( + C(p) • Aortic compliance ) dt SVR dt Systole Heart rate

Parameters of Pulse Contour Analysis Introduction to the PiCCO-Technology – Pulse Contour Analysis Parameters of Pulse Contour Analysis Dynamic parameters of volume responsiveness – Stroke Volume Variation SVmax SVmin SVmean Besides CO, the PiCCO also measures the dynamic parameters of volume responsiveness from the arterial pressure curve. To do this, the stroke volumes are measured over a period of 30 seconds and the stroke volume variation is calculated from this. This gives very reliable information on whether the heart will respond to an increase in preload with an increase in ejection. SVmax – SVmin SVV = SVmean The Stroke Volume Variation is the variation in stroke volume over the ventilatory cycle, measured over the previous 30 second period.

Parameters of Pulse Contour Analysis Introduction to the PiCCO-Technology – Pulse Contour Analysis Parameters of Pulse Contour Analysis Dynamic parameters of volume responsiveness – Pulse Pressure Variation PPmax PPmin PPmean The pulse pressure variation is determined similarly to the stroke volume variation. This too is a reliable parameter of volume responsiveness. PPmax – PPmin PPV = PPmean The pulse pressure variation is the variation in pulse pressure over the ventilatory cycle, measured over the previous 30 second period.

Summary pulse contour analysis - CO and volume responsiveness Introduction to the PiCCO-Technology – Pulse contour analysis Summary pulse contour analysis - CO and volume responsiveness The PiCCO technology pulse contour analysis is calibrated by transpulmonary thermodilution PiCCO technology analyses the arterial pressure curve beat by beat thereby providing real time parameters Besides cardiac output, the dynamic parameters of volume responsiveness SVV (stroke volume variation) and PPV (pulse pressure variation) are determined continuously