Pressure in the pulmonary circulation
Pulmonary artery occlusion pressure
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.
Preload dependency
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) [6, 7]. 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.
Pulmonary capillary pressure
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 [9, 10]. 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.
Continuous measurement of end-diastolic volume and ejection fraction
In the 1980s, technological improvements led to the introduction of the 'volumetric' pulmonary catheter. These catheters differ from the previous version in three different ways [11]. They have two intracardiac electrodes that allow continuous measurement of the patient's electrocardiogram and of the R-R interval (or a connection with cardiac monitoring in more recent devices); they have a rapid response thermistor (response time between 50 and 70 ms); and they have a special injection port that allows more complete distribution throughout the right ventricle.
The 'volumetric' PAC thermodilution curve is processed and the logarithmic decay portion of the curve is calculated on a beat-to-beat analysis, as determined by the intracardiac electrodes. By calculating the residual temperature change between beats, the computer determines the RVEF. The RVEF is then used to calculate the RVEDV, as described in the following equation:
RVEDV = CO/(heart rate [beats/min] × RVEF)
RVEDV should represent a left ventricle preload indicator, but some major problems were identified in the earliest studies. RVEDV was compared with PAOP, which is acknowledged to be a poor indicator of preload dependency. There is mathematical coupling between CO and RVEDV, because the RVEDV index is calculated from stroke volume. This mathematical coupling has been proposed to account for the significant correlation between these two parameters. To overcome this methodological problem, several authors measured CO independently using indirect calorimetry, two different thermodilution technologies, or transoesophageal echocardiography [12, 13]. In those studies, RVEDV remained correlated with CO, and RVEF measured using a 'volumetric' PAC was equivalent to RVEF measured using another method.
That the new, volumetric PAC can measure both RVEF and RVEDV is an important feature. Continuous measurement of RVEF and of RVEDV (CEDV) should be useful in guiding haemodynamic treatment. RVEF reflects the right ventricular contractility and afterload, whereas RVEDV provides information on right ventricular preload. Initial studies found a good correlation between RVED and CO, but in most of them the RVEDV was no different before and after fluid loading, challenging the ability of RVEDV to predict fluid responsiveness [14–17]. However, in two studies indexed RVEDV was significantly lower before than after fluid challenge [18, 19]. Above a value of 138 ml/m2 patients did not respond to further fluid loading with an increase in CO, and under 90 ml/m2 a high percentage of patients were responders to fluid loading. However, between these two values RVEDV index was unable to predict fluid responsiveness. This lack of ability to predict preload dependency was recently confirmed during cardiac surgery in which CEDV was used [20]. The concept of an optimal value of RVEDV was probably an oversimplification of a complex relationship between preload, contractility and afterload. Because of contractility and afterload, RVEF should probably be taken into consideration when interpreting RVEDV. However, if a single value of RVEDV is unable to predict fluid responsiveness, then trends over time should be of interest if they are combined with other parameters from the PAC, particularly continuous CO (CCO) and continuous measurement of SvO2. Right ventricular failure could be another field of interest for CEDV, particularly in guiding treatment.
Cardiac output determination
Thermodilution: the bolus method
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:
Vi(Tb - Ti) (ρiCi/ρbCb) = Q × ∫Tdt
Q = Vi(Tb - Ti) × (ρiCi/ρbCb)/∫Tdt
Where Vi is the volume of injectate, Ti is the temperature of injectate, Tb is the blood temperature, T is the variation in temperature over time, ρi and ρb are the specific gravities of injectate and blood, and Ci and Cb 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 = Vi(Tb - Ti)/S × (ρiCi/ρbCb) × k
Where S is the area under the thermodilution curve and k is the catheter constant.
Despite these correction factors, several methodological limitations persist [3, 22]. 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.
Continuous cardiac output
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) [24–26]. In all studies the bias was acceptable (-0.48 to +0.35 l/min, with precision of 0.56–0.74 l/min) [24–26]. 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].
Mixed venous oxygen saturation
In several studies a drop in SvO2 has been associated with a poorer prognosis after cardiac surgery [28], in severe cardiopulmonary disease [29], and in cardiogenic and septic shock [30, 31]. Therefore, SvO2 monitoring should be of interest in critically ill patients. SvO2 is considered an index of global oxygenation, reflecting the balance between DO2 and oxygen consumption (VO2). The main determinants of SvO2 are VO2, haemoglobin, arterialoxygen saturation (SaO2) and CO. At constant VO2 and with haemoglobin and CO within the normal ranges, there is good correlation between SvO2 and CO. Because the mathematical relationships between SvO2 and its determinants are linear (VO2 and SaO2) or curvilinear (haemoglobin and CO), the weight of these determinants is not the same; the influence of VO2 and SaO2 is independent of their absolute values, but a small decrease in CO in a hyperdynamic state does not induce any change in SvO2. Impaired microcirculation, as occurs in severe sepsis or septic shock, induces a deficit in oxygen extraction so that the SvO2 will not necessarily decrease, even in the presence of an inadequateVO2/DO2 relationship. In this situation a normal SvO2 is not equivalent to adequate organ perfusion. Finally, the SvO2 is a global index of oxygenation, and does not provide information on regional perfusion.
For all of the reasons given above, SvO2 must be interpreted with caution. It is not an index of inadequate CO, and each of the four determinants must be considered. However, whether SvO2 does or does not correlate with CO is not of major importance. In the majority of cases a decrease in SvO2 represents an alert that the global VO2/DO2 relationship is inadequate, regardless of the source of this decrease. For example, even if the drop in SvO2 is secondary to an increase in VO2 (and not to a decrease in CO or DO2) during weaning from mechanical ventilation, this variation in SvO2 must be taken into consideration because it reflects the fact that the cardiorespiratory status of the patient does not fit the new situation. In this example one should consider whether there is a need for transfusion, whether left ventricular failure is present and the respiratory load; postponement of weaning may be necessary [32]. Hence, even when CO is not directly involved in a SvO2 variation, reconsideration of therapeutic approach can ensue.
Continuous measurement of mixed venous oxygen saturation
In several studies, an unexpected drop in SvO2 has been observed following cardiac surgery, emphasizing the potential value of continuous SvO2 monitoring [33, 34]. Measurement of SvO2 has been available since fibreoptics were incorporated into the PAC. Spectrophotometry is the reference technique for measuring oxygen saturation. The absorption spectrum of red blood cells depends on the relative concentrations of oxyhaemoglobin and haemoglobin. Using the continuous method, the emitted light illuminates the blood within the vessel lumen, and is backscattered and refracted by the different blood cells and the vessel wall. The reflected light is retransmitted to a photodetector by one or two bundles of fibreoptics. Depending of the device, two or three wavelengths between the red and infrared domains are used. Oxygen saturation is assumed to be a function of the ratio of reflected light at the various selected wavelengths.
The accuracy of continuous measurement has been tested in vitro and in vivo [35–38]. In both the correlation is good and bias – in those studies that reported it – is small. Ideally, continuous measurement of SvO2 should be done over 24 hours; this avoids significant drift and the need for recalibration. However, several factors have been found to influence the accuracy of the method, namely blood flow velocity, distance between the catheter and the vessel wall, red blood cell shape and refractive index of the plasma [22]. The use of three wavelengths, which is theoretically better at avoiding such disturbances, was not found to be more accurate than using two wavelengths in a clinical study [39].
Taking into account the ratio of benefit to risk with pulmonary artery catheterization, a central venous catheter with continuous monitoring of oxygen saturation (central venous oxygen saturation [ScvO2]) has been developed. Several studies have compared the accuracy of the two methods [40, 41]. In critically ill patients there is a systematic positive shift of between 5 and 8 mmHg in ScvO2 compared with SvO2 [40]. This shift may be explained by a relative increase in cardiac and cerebral blood flow in circulatory failure and a redistribution of blood flow in sepsis associated with a proportionally reduced blood flow in hepatic, splenic, mesenteric and renal territories. In most studies there is a wide range of 95% limits of agreement (when available) in intensive care as well as in anaesthesiology, indicating variability between the two methods [40, 41]. Therefore, individual values of SvO2 and ScvO2 are not equivalent. However, in the same studies [40, 41] the bias was low (<2–3%), indicating that the trends of SvO2 and ScvO2 are similar (Figure 3). Clinical decisions are rarely based on a single measurement of a single parameter. Trends in these parameters and their variations following therapeutic decisions are often more interesting.
If we are to use SvO2 as a parameter for haemodynamic monitoring, then we must define a threshold value. A few years ago, Rivers and coworkers [42] used continuous monitoring of ScvO2 in an early goal-directed therapy algorithm in severe sepsis and septic shock patients. The threshold value of ScvO2 was 70%. That approach was effective; the mortality rate in the early goal-directed therapy group was decreased by 16.7% in comparison with the control group. If we consider the shift of 7 mmHg between SvO2 and ScvO2 in critically ill patients [40], a SvO2 threshold of around 65% should be used in further studies.