**3. Background to main methods**

#### **3.1. Bioimpedance**

In 1957 Nyboer made the observation that the cardiac cycle was associated with repetitive changes in thoracic impedance and that stroke volume could be estimated from the area under the curve of the resulting impedance waveform. In 1966 Kubicek applied this observation to developing a method that could measure cardiac output in space by astronauts. Later he developed the first commercial impedance cardiograph, the Minnesota [11]. In the 1980's the BoMed NCCOM3 (BoMed Ltd., Irvine, CA, USA) (Figure 1) was developed by Bernstein and Sramek [12]. It used a modified Kubicek method to calculate cardiac output. It also automated the process calculating cardiac output, and provided continuous cardiac output readings in real-time. Thus, the first continuous MICOM had been developed.

**3.2. Doppler ultrasound**

**3.3. Pulse contour analysis**

sterdam, Netherlands).

**3.4. Other methods**

Ultrasound was first described in 1842. It was introduced into clinical practice in the 1950s by Ian Donald, a Scotsman. Echocardiography was developed in 1960's and used pulsed ultra‐ sound for imaging. The measurement of blood flow using Doppler ultrasound was developed later to detect aortic and peripheral blood flow using continuous wave Doppler systems. In the 1980's Singer a London critical care physician was instrumental in the clinical development of oesophageal Doppler cardiac output monitoring [18]. In the early 1990's several prototype monitor and probe systems were developed such as the Hemosonic 1000, (Arrow Internation‐ al, Reading, PA, USA), and the Abbott ODM II, (Abbott Laboratories, Chicago, Il, USA). The only successful model has been the CardioQ, (Deltex Medical, Chichester, England) released in the early1990's. In early 2000 an external continuous wave Doppler system was developed called the USCOM, (USCOM Ltd., Sydney, Australia). Previously one had to use echocardiog‐ raphy machines with limited Doppler capabilities for external monitoring. The USCOM meas‐ ures cardiac output from both the ascending aorta and pulmonary artery using a hand held probe placed over the anterior neck (i.e. thoracic inlet) or left anterior chest wall (i.e. 3th to 5th in‐

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Noninvasive continuous blood pressure measurement using a pneumatic finger cuff (i.e. plethysmography) was developed over 30-year ago. In 1993 Wesseling et al described a method of using the finger cuff arterial pressure wave to derive cardiac output [19]. Their method known as "Model Flow" was incorporated into the Finapres series of noninvasive continuous blood pressure monitors. Currently, the manufacturers produce the Nexfin, (BMEYE, Am‐

Systems that used the arterial blood pressure trace to measure cardiac output were later devel‐ oped. In 1997 the first commercial system, the PiCCO (Pulsion, Munich, Germany) was re‐ leased. The PiCCO was calibrated using transpulmonary thermodilution and monitored cardiac output from a femoral arterial line. Since, several other systems have been developed including in 2002 the LiDCO-plus (and later rapid), (LiDCO Ltd., Cambridge, England), and in 2004 the FloTrac-Vigileo, (Edwards Lifesciences, Irvine, CA, USA). Early versions of these monitors relied on external calibration, usually by thermodilution. However, more recent ver‐ sions self-calibrate using patient demographic data. Pulse contour monitoring of cardiac out‐ put has not proved all that successful and current systems are unreliable when large fluctuations in peripheral resistance occur [20]. Recently there has been a change in the market‐ ing policy. The focus is now towards "functional haemodynamic variables", such as pulse

pressure and stroke volume variation in response to fluid and postural challenges.

Several other novel techniques of measuring cardiac output have also been developed. In the 1970's researchers explored the possibility of using the mechanical impulse produced by heart as it contracted. In the 1990's a modified Fick method based on carbon dioxide rebreathing

tercostals spaces). Thus, the USCOM measures cardiac output intermittently.

**Figure 1.** The BoMed NCCOM3. It connects to the patients using eight skin surface electrodes applied to the mid-neck and lower chest at the level of the diaphragm. Two additional ECG electrodes can be added. The BoMed is calibrated by inputting the patient's height and weight. Cardiac output and related bioimpedance variables are displayed as numbers. Data is averaged over 16 heart-beats.

Unfortunately, the BoMed had problems with its reliability and was never was accepted into clinical practice [13]. The presence of lung fluid corrupted impedance readings [14,15] and it was never determined with any certainty what the BoMed actually meas‐ ured [16]. A digitalized version is still marketed and called the BioZ (CardioDynamics, San Diego, CA, USA). A number of companies have tried over the years to produce a more reliable version, but none have been very successful [17]. There is a haemodynamic monitoring system that incorporates bioimpedance cardiac output as one of its modali‐ ties call the Task-Force Monitor (CNSystems, Graz, Austria). It is used mainly to study autonomic responses such as syncopy and head up tilting. There is also a device on the market called the NICOM (Cheetah Medical Ltd., Tel-Aviv, Israel) that uses a principle call bioreactance, which measures shifts in alternating current phase, rather than electri‐ cal resistance. Potentially, this device may be immune to the problems that afflicted the BoMed, but good validation data are still needed.
