The pulmonary artery occlusion pressure (PAOP) is obtained following inflation of the balloon at the tip of the PAC. In theory, after inflation of the balloon there is a continuous column of blood from the pulmonary artery to the left ventricle during diastole. The end of the diastole can be identified by the 'a' wave of the PAOP curve, which coincides with the 'p' wave on the electrocardiogram. Consequently, PAOP is considered an approximation of the left ventricular end-diastolic pressure (LVEDP) 3. For a given left ventricular compliance, LEVDP is proportional to the left ventricular end-diastolic volume (LVEDV). As described by the Frank–Starling relationship, the force of ventricular contraction is proportional to the length of the myocardial fibres, as determined by LVEDV. Therefore, PAOP can be considered an indicator of preload.

Knowledge of preload is fundamental to clinical practice in intensive care or during surgery. For example, when other haemodynamic parameters (e.g. SvO₂, serum lactate concentration, or renal function) suggest to the clinician that tissue perfusion must be improved via increased oxygen delivery (DO₂), preload determination allows the clinician to choose between fluid loading and inotropic drugs. In other pathologies, such as left ventricular failure or ARDS, preload must be controlled to avoid worsening of pulmonary oedema.

However, the assumption that pulmonary artery occlusion always induces a continuous blood column may not be valid in some cases (Figure 1). First, when the catheter tip is in West zone 1 or 2, the increase in alveolar pressure interrupts the blood column. Consequently, PAOP is higher than end-diastolic pulmonary pressure and pulmonary venous pressure. To address this problem, the catheter tip must be in West zone 3. If this is the case, then the following relationship will be present during the respiratory cycle in mechanically ventilated patients 4: end-diastolic pulmonary pressure > PAOP, and ΔPAOP/ΔPAP > 1.5 (where PAP is the pulmonary artery pressure). Second, in mitral valve disease PAOP reflects the increase in left atrial pressure and not the LVEDP. In mitral stenosis the PAOP trace has a large 'a' wave and in mitral regurgitation a large 'v' wave. Finally, all changes in ventricular compliance (the LVEDP/LVEDV relationship) induce overestimation of preload by PAOP. Modification to left ventricular compliance may result from numerous pathologies, including myocardial ischaemia and failure, myocardial hypertrophy or dilatation, septic chock, aortic disease and pericardial disease.

Despite these practical limitations, PAOP provides some useful information. When dynamic preload dependency indicators (see below in this paragraph) are unreliable (i.e. in the presence of arrhythmia or spontaneous ventilation, among other conditions), it is always possible to establish a Frank–Starling relationship between PAOP and stroke volume variation (or CO) following successive fluid challenges. The stroke volume does not increase any further after additional fluid challenge when the flat part of the Frank–Starling curve is reached, indicating preload independency. In pulmonary arterial hypertension a difference (>7–8 mmHg) between diastolic PAP and PAOP indicates an increase in pulmonary artery (or capillary) resistance, and primary pulmonary hypertension is diagnosed. In contrast, pulmonary arterial hypertension without any gradient is secondary to increased pulmonary venous resistance, and causes of altered left ventricular compliance (e.g. myocardial ischaemia or left ventricular failure) or mitral disease must be explored.

Right atrial pressure and central venous pressure have largely been used as static preload indicators. During the past decade, however, several dynamic indicators for preload dependency such as pulse pressure variation or Δdown have been studied. In most of these studies, these parameters were compared with the classic static parameters such as PAOP or central venous pressure 5. Compared with dynamic indicators, static parameters have poor ability to predict responsiveness to fluid challenge, except when they are very low (less than 5 mmHg) 67. Static parameters cannot therefore be recommended as indicators of preload dependency, and PAOP cannot be used as a first-line tool to make fluid loading decisions if dynamic parameters are available.

Dynamic parameters also have limitations in settings such as cardiac arrhythmia, spontaneous ventilation, high-dose vasopressors and right ventricular failure. Dynamic indices are unable to predict volume of fluid challenge and tolerance to a subsequent fluid challenge when the patient's volume status is on the upper part of the slope of the Frank–Starling relationship. In this setting the PAOP remains a good indicator of fluid challenge tolerance; a large increase in PAOP (5–10 mmHg) after one fluid challenge indicates that further fluid loading should be considered with caution. Fluid responsiveness is a better basis for decisions regarding fluid loading; however, it is not equivalent to fluid loading tolerance. Therefore, static and dynamic preload parameters provide complementary information.

As described above, increased gradient between PAOP and diastolic PAP indicates increased pulmonary resistance or increased pulmonary blood flow, or both. In these settings, pulmonary capillary pressure (Pcp) may exceed PAOP 8. Therefore, an increased gradient between diastolic PAP and PAOP is considered a valuable indicator of increased Pcp. The resistance between pulmonary artery and left atrium can be simply modelled as one artery resistance and one venous resistance in series, with a capacitance located in the capillary bed 910. Because of this series resistance with a capillary capacitance, the Pcp can be measured from the pressure decay profile after occlusion of the balloon (Figure 2). After occlusion of the pulmonary artery, the downstream blood is discharged into the capillary across arterial resistance and then into the pulmonary veins across venous resistance 8. The initial rapid drop in pressure reflects the Pcp as the downstream blood is trapped in the capillary bed and equilibrates with the Pcp. The following slower drop in pressure is determined by the discharge of blood across the pulmonary venous resistance and tends toward the PAOP (Figure 2).

The more sophisticated approach to determining the Pcp includes the average smoothing of the pressure signal and mathematical curve fitting of the signal. With an approach that is more realistic at the bedside, the Pcp can be measured using a graphical method; the Pcp is estimated as the point at which the pressure curve deviates from the slope of the first rapid decay (Figure 2).

Because Pcp is the main determinant of efflux between capillary lumen and alveolar space, whether the integrity of alveolar–capillary barrier is impaired or not, its measurement may be of interest in pathologies such as ARDS to guide fluid loading 8. A Pcp threshold value must be determined above which pulmonary oedema develops, and pulmonary compliance and gas exchange are impaired. Fluid loading should be then limited to this threshold value as much as possible, taking into consideration the perfusion of other organs. Further studies are evidently necessary to explore the utility of such a strategy and to develop new tools for automatic measurement of Pcp.

Measurement of CO using a PAC is based on the injection of tracer into the right atrium and analysis of the change in its concentration in the pulmonary artery. If it is assumed that the mass (M) of tracer is constant, then it has been shown that M is equal to the product of the blood flow (Q) and its concentration over time (C), as expressed in the Stewart–Hamilton equation.

M = Q × ∫C(t)dt

Currently, the tracer usually used is an injection of cold solution in the right atrium. The temperature variation is monitored in the pulmonary artery. The above equation can be expressed as follows:

V_i(T_b - T_i) (ρ_iC_i/ρ_bC_b) = Q × ∫Tdt

Q = V_i(T_b - T_i) × (ρ_iC_i/ρ_bC_b)/∫Tdt

Where V_i is the volume of injectate, T_i is the temperature of injectate, T_b is the blood temperature, T is the variation in temperature over time, ρ_i and ρ_b are the specific gravities of injectate and blood, and C_i and C_b and the specific heats of injectate and blood.

The final Stewart–Hamilton equation includes a correction factor that depends on the type of catheter used 21:

Q = V_i(T_b - T_i)/S × (ρ_iC_i/ρ_bC_b) × k

Where S is the area under the thermodilution curve and k is the catheter constant.

Despite these correction factors, several methodological limitations persist 322. First, heat transfer to right atrium blood, wall and surrounding tissue lead to overestimation of CO. Intracardiac shunts, baseline temperature variation in pulmonary artery blood, abnormal haematocrit and cardiac arrhythmia are other sources of errors. Second, conditions surrounding the injectate infusion may represent a further source of error. A 10 ml injectate at room temperature seems adequate in most circumstances (2.6–4.2 l/min per m²), but cold injectate is recommended in low flow and hyperdynamic states. Variations in volume and speed of the cold tracer infusion can induce differences between measurements. Mechanical ventilation induces complex variations in CO, which depend on the clinical situation. For all of these reasons, variations between two single measurements of up to 25% can occur, and it is therefore recommended that a minimum of three bolus measurements throughout the respiratory cycle be averaged. The variation between two series of three measurements is reduced to 15%. A third methodological limitation is that rapid change in temperature induced by rapid fluid administration (>1 l/hour), use of an upper body warming blanket and extracorporeal oxygenation decrease the accuracy of CO measurement. Finally, in tricuspid regurgitation the transit time of the tracer is increased and the temperature is modified by regurgitation of blood into the right atrium. Therefore, tricuspid regurgitation can induce overestimation or underestimation of CO.

In contrast to intermittent thermodilution, the tracer used for CCO is not cold but warm. A 10 cm thermal filament is inserted into the catheter at the level of the right ventricle. The surface temperature of the filament is always below 44°C. Low levels of heat energy are transferred to the blood according to a pseudo-random binary sequence. A cross-correlation based on the input sequence and the downstream signal measured by the thermistor is performed. The heat signal is processed over time and the classical thermodilution curve is rebuilt. CO is determined using a modified Stewart–Hamilton equation. The CO value is an average over a 3 min period (minimum) 22 and not a beat-to-beat measurement. It is an 'almost' continuous CO measurement.

In vitro studies found good accuracy but with a systematic trend toward overestimation 23. The degree of overestimation is nevertheless lower with CCO than with the bolus method 23. CCO has been evaluated in humans in comparison with reference methods such as the Fick method, dye dilution (indocyanin green) and electromagnetic measurement of aortic blood flow (often considered the 'gold standard' in the cardiac laboratory) 242526. In all studies the bias was acceptable (-0.48 to +0.35 l/min, with precision of 0.56–0.74 l/min) 242526. Accuracy of the bolus method is lower with very high and very low CO. The classical limitations of thermodilution also apply to CCO monitoring, but because the CCO value represents an average of measurements made over a period of time, it might be expected that increasing the integration period of the signal could decrease the influence of the usual factors that limit the thermodilution technique, such as tricuspid regurgitation, cardiac arrhythmia and baseline variation of pulmonary artery blood, among others. When compared with the bolus method, CCO determination has negligible bias but exhibits better reproducibility, probably because CCO monitoring avoids interindividual variations in volume and speed of infusion of the tracer bolus 27.