**3. Cardiac output**

With a definition of normovolaemia based on the ability of the heart to establish an adequate flow, CO is of interest. As mentioned, patients undergoing OLT present a large CO while MAP may be low (el-Masry *et al.*, 2009; Ejlersen *et al.*, 1997). Yet MAP often normalises when the blood volume, and hence CBV, is expanded to an extent that it does not limit CO, i.e. the patients are provided with the CBV that healthy subjects are provided with when supine (Harms *et al.*, 2003). However, significant ascites may affect venous return to the heart by pressure on the inferior caval vein that can be relieved by tilting the patient to the left - as known from women before birth - but that pressure is eliminated as the abdominal cavity is opened at start of surgery. As indicated, however, OLT is associated with significant changes in the cardiovascular system from the dissection phase to the anhepatic phase and following reperfusion of the donor liver and CO normalises only slowly by the end of the operation (Table 1).

To attenuate a reduction in venous return to the heart from the clamped inferior caval vein during the hepatectomy and insertion of the donated liver and thereby stabilize CO, an extra-corporeal veno-venous bypass shunt (VVBP) can secure portal and femoral venous drainage to one or two veins on the arm or to a central venous access (Ozier & Klinck, 2008). Veins on the arm are preferred to central veins to avoid that blood accumulates in the mediastinum in the case the catheter(s) has perforated the vein(s). Before a central vein receives blood from the shunt, it needs to be secured that blood can be aspirated from the catheter. The VVBP has a flow of 1.5-3 l/min, but for children and patients with a portal hypertension, venous return to the heart may be maintained by spinal and abdominal veins and veins along the oesophagus and there may, accordingly, be no need for a VVBP in these patients accepting substantial accumulation of blood in the splanchnic region. Yet surgical bleeding may be reduced if blood does not accumulate in distended abdominal veins.

At any rate, blood accumulates in the splanchnic region while the portal vein is clamped for establishing the VVBP and when it is seponated the accumulated amount of blood helps to fill the donor liver. Alternatively, the "piggyback" technique for which the inferior caval vein is side-clamped can reduce the restrain on venous return to the heart during the hepatectomy and surgery on the vessels to the donor liver. Notably, stability of the circulation is secured if reperfusion of the liver is graded by declamping the caval vein above the liver followed by declamping the vein below the liver and thereafter establishing its arterial flow.

#### **3.1 Monitoring of cardiac output**

For monitoring of CO several methods are applicable and not all will be addressed here. Ideally the chosen method should be reliable, continuous, and easy to set-up and to use and

fluid load may be required than that which establishes that the patient has been provided with a normal blood volume. For additional volume threatment of patients, the administration of lactated Ringer solution is preferable to the administration of saline

With a definition of normovolaemia based on the ability of the heart to establish an adequate flow, CO is of interest. As mentioned, patients undergoing OLT present a large CO while MAP may be low (el-Masry *et al.*, 2009; Ejlersen *et al.*, 1997). Yet MAP often normalises when the blood volume, and hence CBV, is expanded to an extent that it does not limit CO, i.e. the patients are provided with the CBV that healthy subjects are provided with when supine (Harms *et al.*, 2003). However, significant ascites may affect venous return to the heart by pressure on the inferior caval vein that can be relieved by tilting the patient to the left - as known from women before birth - but that pressure is eliminated as the abdominal cavity is opened at start of surgery. As indicated, however, OLT is associated with significant changes in the cardiovascular system from the dissection phase to the anhepatic phase and following reperfusion of the donor liver and CO normalises only slowly by the end of the

To attenuate a reduction in venous return to the heart from the clamped inferior caval vein during the hepatectomy and insertion of the donated liver and thereby stabilize CO, an extra-corporeal veno-venous bypass shunt (VVBP) can secure portal and femoral venous drainage to one or two veins on the arm or to a central venous access (Ozier & Klinck, 2008). Veins on the arm are preferred to central veins to avoid that blood accumulates in the mediastinum in the case the catheter(s) has perforated the vein(s). Before a central vein receives blood from the shunt, it needs to be secured that blood can be aspirated from the catheter. The VVBP has a flow of 1.5-3 l/min, but for children and patients with a portal hypertension, venous return to the heart may be maintained by spinal and abdominal veins and veins along the oesophagus and there may, accordingly, be no need for a VVBP in these patients accepting substantial accumulation of blood in the splanchnic region. Yet surgical bleeding may be reduced if blood does not accumulate in distended abdominal

At any rate, blood accumulates in the splanchnic region while the portal vein is clamped for establishing the VVBP and when it is seponated the accumulated amount of blood helps to fill the donor liver. Alternatively, the "piggyback" technique for which the inferior caval vein is side-clamped can reduce the restrain on venous return to the heart during the hepatectomy and surgery on the vessels to the donor liver. Notably, stability of the circulation is secured if reperfusion of the liver is graded by declamping the caval vein above the liver followed by declamping the vein below the liver and thereafter establishing

For monitoring of CO several methods are applicable and not all will be addressed here. Ideally the chosen method should be reliable, continuous, and easy to set-up and to use and

(Waters et al., 2001).

**3. Cardiac output** 

operation (Table 1).

veins.

its arterial flow.

**3.1 Monitoring of cardiac output** 

at the same time possess the capability for a fast response time. Of these priorities, the accuracy of the absolute value is of least relevance due to the marked inter-individual variations in CO among the patients, e.g. 2.5 to 17 l min-1 (Nissen *et al.*, 2009b) and the often 2-fold change in CO during the operation, but the method should be able, at all times, to report the changes in CO faithfully and most importantly so during reperfusion of the grafted liver.

A pulmonary artery catheter (PAC) determines CO by thermodilution based on the Henriques-Stewart-Hamilton equation (Pinsky, 2007) and is for clinical use regarded as the golden standard, but it then requires an average of three or probably four determinations (Nilsson et al., 2004) based on bolus injection of (10 ml) cooled saline. Furthermore, it remains a problem that the baseline temperature is often too unstable to make a thermodilution determination of CO possible within the first minutes after reperfusion of the grafted liver. That problem is exaggerated with the version of PAC that uses heating filaments for "continuous" CO determination because the appreciated change in temperature is small and it may take 15 –20 min, or more, after reperfusion of the grafted liver before such a CO can be determined (De Wolf, 2006; Bao & Wu, 2008).

The advantage of transoesophageal echocardiography (TEE) is that it provides a real-time image of the heart and thereby on-line information not only about filling of the heart but also about the structure and contractility of the myocardium (Della *et al.*, 2009) of relevance especially during reperfusion of the grafted liver in case CO does not increase. Thus, TEE allows for distinction between a need for administration of volume versus sympatomimetic drugs. Unfortunately, however, mainly cardiac anaesthesiologists are familiar with the use of TEE and it remains a concern that TEE requires high costs and a need for training (Della *et al.*, 2009). It should also be mentioned that although individualized goal directed fluid administration aims at filling the heart with blood (Figs. 1 and 2), a detailed TEE evaluation of whether that is the case requires off-line evaluation.

Studies comparing CO determined by transoesophageal echo-Doppler (TED) against PAC show conflicting results (Shimamoto et al., 1992; Boucaud et al., 2008; Laupland & Bands, 2002; Colbert et al., 1998) although there seems to be agreement to that changes in CO are reflected by TED. A disadvantage with TED is, however, frequent dislocation of the ultrasound probe (Lefrant et al., 1998) of relevance for the in general long-lasting OLT and TED is counter-indicated in patients with oesophageal disorders of relevance for many of the OLT patients and once a Doppler probe is in place it hinders TEE (de Waal *et al.*, 2009).

For continuous recording of CO, several methods appreciate the arterial waveform. The PiCCO and LiDCO generate a continuous CO by analysis of the arterial pulse pressure (PP). For both methods, an independent technique is used to calibrate the continuous CO analysis since the arterial pulse-pressure analysis does not account for variables such as changing compliance of the vascular bed. Recalibration of CO is recommended after changes in patient position, therapy, or condition (de Waal *et al.*, 2009) of relevance for OLT encompassing marked changes in the vasculature through the different phases of the operation.

In the case of PiCCO, transpulmonary thermodilution is used for calibration. As with the PAC, PiCCO appreciates transpulmonary thermodilution according to the Henriques-Stewart-Hamilton principle but considers that a determination of a change in temperature from a central venous line to an arterial line (e.g. femoral or axillary) is less invasive than a determination based on a PAC catheter. The CO derived from this cold-saline thermodilution is used to calibrate the arterial pulse-pressure contour that then provides the continuous CO. The PiCCO algorithm appreciates the blood pressure waveform morphology (i.e. mathematical analysis of the pulse-pressure waveform) and calculates a continuous CO as described by Wesseling et al (Wesseling *et al.*, 1993). Transpulmonary thermodilution includes both the right and left side of the heart as well as the pulmonary circulation and that allows for further analysis of the thermodilution curve with measures of the cardiac filling volume, the intrathoracic blood volume, and the extravascular lung water, the latter addressing wheather pulmonary oedema is developed (Oren-Grinberg, 2010; Costa *et al.*, 2007). Accepting that transpulmonary thermodilution may be a less invasive procedure for determination of CO than one based on PAC, it is also less accurate and still requires central venous and arterial lines.

In the case of LiDCO, the independent calibration technique is lithium dilution, again according to the Henriques-Stewart-Hamilton principle. LiDCO uses lithium dilution from a peripheral vein to an arterial line and, thereby, does not express information on cardiac filling volumes or the extravascular lung water. It is also a concern that calibration cannot be performed frequently and calibration may be unreliable in patients with grave hyponatreamia (Morgan et al., 2008) that may manifest in some OLT patients. The PulseCO algorithm used by LiDCO is based on pulse power derivation rather than on waveform morphology.

Continuous tracking of changes in stroke volume by arterial pulse wave analysis in Modelflow provides flow from pressure and has the potential to appreciate the importance of systemic blood flow (Wesseling *et al.*, 1993;Harms *et al.*, 1999). With Modelflow®, beat-tobeat CO is estimated from the arterial pressure wave (Wesseling *et al.*, 1993). Pressure from an arterial line is, after calibrating and zeroing to the mid-axillary level used as input to the model to calculate CO. The method uses a non-linear three-element model of the aortic input impedance and simulates the aortic flow waveform from the pressure signal. Two of the three model elements (aortic characteristic impedance and arterial compliance) depend on the elastic properties of the aorta and are computed using a built-in database of arctangent aortic pressure-area relationships given age and gender of the patient. Integrating the aortic flow waveform per beat provides left ventricular stroke volume and CO is the product of stroke volume and HR while the third model element, peripheral vascular resistance is calculated for each heartbeat as the quotient of arterial pressure to CO (Fig. 3A). The software used is an online real-time version of Beatscope® (FMS, Amsterdam, The Netherlands).

The Modelflow method is fully automatic, self-recording, has a fast response time, a high precision, and has been successfully validated against a thermodilution estimate of CO during cardiac surgery (Jansen *et al.*, 2001), intensive care medicine (Jansen *et al.*, 2001;Jellema *et al.*, 1999), and notably during OLT (Nissen *et al.*, 2009b) and, surprisingly, without a need for taking potential differences in vascular tone during the operation into account (Fig. 3 B). That is the case although Modelflow appears to underestimate deviations in CO during manipulation of body temperature with a significant increase in vascular conductance during heating (Shibasaki *et al.*, 2011).

#### **4. Thoracic electric admittance**

With the large spontaneous changes in CO during OLT, it may be an advantage to monitor CBV separately and, as indicated, evaluate the pulmonary water content. According to

thermodilution is used to calibrate the arterial pulse-pressure contour that then provides the continuous CO. The PiCCO algorithm appreciates the blood pressure waveform morphology (i.e. mathematical analysis of the pulse-pressure waveform) and calculates a continuous CO as described by Wesseling et al (Wesseling *et al.*, 1993). Transpulmonary thermodilution includes both the right and left side of the heart as well as the pulmonary circulation and that allows for further analysis of the thermodilution curve with measures of the cardiac filling volume, the intrathoracic blood volume, and the extravascular lung water, the latter addressing wheather pulmonary oedema is developed (Oren-Grinberg, 2010; Costa *et al.*, 2007). Accepting that transpulmonary thermodilution may be a less invasive procedure for determination of CO than one based on PAC, it is also less accurate and still

In the case of LiDCO, the independent calibration technique is lithium dilution, again according to the Henriques-Stewart-Hamilton principle. LiDCO uses lithium dilution from a peripheral vein to an arterial line and, thereby, does not express information on cardiac filling volumes or the extravascular lung water. It is also a concern that calibration cannot be performed frequently and calibration may be unreliable in patients with grave hyponatreamia (Morgan et al., 2008) that may manifest in some OLT patients. The PulseCO algorithm used by LiDCO is based on pulse power derivation rather than on waveform morphology.

Continuous tracking of changes in stroke volume by arterial pulse wave analysis in Modelflow provides flow from pressure and has the potential to appreciate the importance of systemic blood flow (Wesseling *et al.*, 1993;Harms *et al.*, 1999). With Modelflow®, beat-tobeat CO is estimated from the arterial pressure wave (Wesseling *et al.*, 1993). Pressure from an arterial line is, after calibrating and zeroing to the mid-axillary level used as input to the model to calculate CO. The method uses a non-linear three-element model of the aortic input impedance and simulates the aortic flow waveform from the pressure signal. Two of the three model elements (aortic characteristic impedance and arterial compliance) depend on the elastic properties of the aorta and are computed using a built-in database of arctangent aortic pressure-area relationships given age and gender of the patient. Integrating the aortic flow waveform per beat provides left ventricular stroke volume and CO is the product of stroke volume and HR while the third model element, peripheral vascular resistance is calculated for each heartbeat as the quotient of arterial pressure to CO (Fig. 3A). The software used is an online real-time version of Beatscope® (FMS, Amsterdam,

The Modelflow method is fully automatic, self-recording, has a fast response time, a high precision, and has been successfully validated against a thermodilution estimate of CO during cardiac surgery (Jansen *et al.*, 2001), intensive care medicine (Jansen *et al.*, 2001;Jellema *et al.*, 1999), and notably during OLT (Nissen *et al.*, 2009b) and, surprisingly, without a need for taking potential differences in vascular tone during the operation into account (Fig. 3 B). That is the case although Modelflow appears to underestimate deviations in CO during manipulation of body temperature with a significant increase in vascular

With the large spontaneous changes in CO during OLT, it may be an advantage to monitor CBV separately and, as indicated, evaluate the pulmonary water content. According to

requires central venous and arterial lines.

The Netherlands).

conductance during heating (Shibasaki *et al.*, 2011).

**4. Thoracic electric admittance** 

Fig. 3. a) Diagram of the three-element non-linear, self-adapting model (right) and input pressure and simulated flow pulse (left) used for Modelflow. Arterial pressure *p* is applied to the model input. *Z*o, characteristic impedance of the proximal aorta; *C*w, arterial Windkessel compliance; *R*p total systemic peripheral resistance. The non-linear properties of *Z*0 and *C*<sup>w</sup> are indicated by a stylised "S" symbol. *R*p has an arrow indicating that it adapts to changes in systemic resistance. The result of the model simulation is a flow curve *q*. Integrated per beat (area under the curve) yields stroke volume. (From Wesselring et al. 1993 with permission). b) Cardiac output followed by Modelflow (MCO) and thermodilution (TDCO) during liver transplantation surgery. (From Nissen et al., 2009 b with permission)

Ohm's law changes in CBV can be assessed by thoracic electrical admittance (TA) and the obtained value is expressed in milli-Siemens (mS). Using a low (e.g. 1.5 kHz) and a high frequency current (e.g. 100 kHz), TA distinguishes between the extracellular (TA1.5) and total water (TA100) content. Accordingly, changes in the difference between the high and the low frequency current reflects those in the intracellular water content (TAICW) (Cai *et al.*, 2000), i.e. red cell volume within the thoracic region (Fig. 4) and TAICW can, thereby, indicate a need for transfusion of blood while TA1.5 monitors the (pulmonary) water content.

With the use of goal-directed approach to the administration of fluid and blood information about CBV becomes important in the anhepatic phase of OLT when approximately one third of the circulation is eliminated causing a similar decrease in CO (Table 1), not necessarily due to hypovolaemia. Similarly when the donor liver is reperfused, an increase in CO requires that CBV is maintained despite the blood needed to fill the liver, while care is directed also to avoid distension of the liver by administrating a too large volume load.

With TA, evaluation of CBV is continuous with the use of, e.g. two ECG electrodes on the right side of the neck and two other electrodes placed high in the midaxillay line on the left side of the thorax (Ejlersen *et al.*, 1997;Matzen *et al.*, 1991) in order to include the heart and central vessels in the evaluation and at the same time exclude the abdominal fluid content. With a four electrode arrangement, skin resistance is eliminated from the evaluation making changes in TA an almost perfect report of those in the thoracic fluid / blood volume (Krantz *et al.*, 2000). Similarly, it is possible to monitor accumulation of blood in the legs during cross-clamping of inferior caval vein by changes in TA over one leg or the glutal region (Ejlersen *et al.*, 1997).

Fig. 4. At low and high frequencies, thoracic electric admittance (TA) distinguishes between the extracellular (ECW) and total body water (TBW). The difference reflects the intracellular water content (ICW) and changes respond to haemorrhage versus administration of blood

When volume is administered according to individualised goal directed fluid therapy, an increase in TA reflects that CBV is increased, as does pulmonary artery mean and wedge pressures and that is the case although there may be no changes in HR, central venous pressure (CVP), or MAP as CO increases during OLT (Ejlersen *et al.*, 1995b).

### **5. Venous saturation**

For continuous reading of SvO2, a PAC catheter is ideal but a central SvO2 may be similarly obtained from a central venous line using a catheter with the same type of fiberoptic oxymeter. Central SvO2 values are about 5% larger than those obtained from the PAC catheter (Krantz *et al.*, 2005; Rivers, 2006) but with parallel changes in response to deviations in blood volume (el-Masry *et al.*, 2009; Krantz *et al.*, 2005). Alternatively, SvO2 may be obtained by blood sampling during the different phases of the operation or, eventually, at times when there is a need to check volume administration during a major blood loss.

Thus, in order to evaluate whether a hypotensive incident is due to a reduced CO or to a reduced afterload, monitoring of SvO2 is well suited (Fig. 2). Considering that the patient's (basal) metabolic rate (Vo2) does not change during the operation (despite the hepatectomy), there is a direct relationship between SvO2 and CO as described by Fick's equation: (Vo2 = (Ca – Cv) Q), where Ca and Cv represent the arterial and venous oxygen content. Therefore, a continuous recording of SvO2 may be applied in situations where devices for continuous recording of stroke volume or CO are not available of relevance, as mentioned, especially for the first minutes after reperfusion of the donor liver. Typically, a low arterial pressure reflects a blood loss in the dissection phase of the operation, while reperfusion of the liver is likely to be associated with a low blood pressure due to loss of peripheral resistance as detected by an increase in muscle blood flow as recorded easily by an increase in muscle oxygenation (SmO2). Surprisingly, also CBF increases during reperfusion of the grafted liver despite MAP may decrease to a level that is lower than normally considered to represent the lower level of cerebral autoregulation (60 mmHg) and an increase in the arterial carbon dioxide tension (PaCO2) seems only partly to explain an elevated CBF during reperfusion of the liver (Pott *et al.*, 1995; Larsen *et al.*, 1999). However, during reperfusion of the liver, function of the heart may be affected by a lowering of HR in response to an abrupt increase in plasma potassium as detected by blood sampling or indicated by the ECG and before the liver is reperfused, a small dose of adrenaline (4-6 μg kg-1 h-1) prevents this slowing of the heart since adrenaline promotes clearance of potassium from the circulation (Struthers et al., 1983) besides its chronotropic effect.

Generally, a reduction in SvO2 should be considered as an indication for a low CO due to hypovolaemia and treated accordingly by applying the principles of individualised goal directed fluid therapy. That is the case although with the often marked increase in CO during early reperfusion of the grafted liver, SvO2 may reach extreme values (>95%) and, as mentioned, TA can indicate whether CBV is maintained or whether further volume treatment would be likely to increase CO even more and thereby stabilize MAP. Thus SvO2 values derived from either a PAC or a central venous catheter have potential as variables for goal directed fluid therapy (Fig. 2) although outcome and comparative studies are available only in regard to monitoring stroke volume or CO (Bundgaard-Nielsen *et al.*, 2007a).

#### **6. Vascular pressures**

368 Liver Transplantation – Basic Issues

of the circulation is eliminated causing a similar decrease in CO (Table 1), not necessarily due to hypovolaemia. Similarly when the donor liver is reperfused, an increase in CO requires that CBV is maintained despite the blood needed to fill the liver, while care is directed also to avoid distension of the liver by administrating a too large volume load.

With TA, evaluation of CBV is continuous with the use of, e.g. two ECG electrodes on the right side of the neck and two other electrodes placed high in the midaxillay line on the left side of the thorax (Ejlersen *et al.*, 1997;Matzen *et al.*, 1991) in order to include the heart and central vessels in the evaluation and at the same time exclude the abdominal fluid content. With a four electrode arrangement, skin resistance is eliminated from the evaluation making changes in TA an almost perfect report of those in the thoracic fluid / blood volume (Krantz *et al.*, 2000). Similarly, it is possible to monitor accumulation of blood in the legs during cross-clamping of inferior caval vein by changes in TA over one leg or the glutal region

Fig. 4. At low and high frequencies, thoracic electric admittance (TA) distinguishes between the extracellular (ECW) and total body water (TBW). The difference reflects the intracellular water content (ICW) and changes respond to haemorrhage versus administration of blood

When volume is administered according to individualised goal directed fluid therapy, an increase in TA reflects that CBV is increased, as does pulmonary artery mean and wedge pressures and that is the case although there may be no changes in HR, central venous

For continuous reading of SvO2, a PAC catheter is ideal but a central SvO2 may be similarly obtained from a central venous line using a catheter with the same type of fiberoptic

pressure (CVP), or MAP as CO increases during OLT (Ejlersen *et al.*, 1995b).

(Ejlersen *et al.*, 1997).

**5. Venous saturation** 

Monitoring arterial pressure is often by way of a catheter in the radial artery, but in case of central hypovolaemia, the radial artery constricts to dilate again as the hypovolaemic shock develops (Iversen et al., 1995) making the pressure in the radial artery a potential underestimate of the systemic pressure (De Wolf, 2006; Krenn & De Wolf, 2008). In contrast, the use of a femoral artery catheter is reliable for recording of MAP (Arnal et al., 2005) but never the less, a radial artery catheter can be used for blood sampling and as back-up for the determination of MAP. For example in case the hepatic artery needs to be grafted to the aorta, partial or complete clamping of the abdominal aorta may eliminate pressure recording in the femoral artery.

The CVP is often taken to express filling of the right ventricle but CVP is not well correlated with preload to the heart as expressed by its diastolic filling (De Wolf, 2006). A correlation between CO and CVP is established during acute changes in the CBV as induced by headup-tilt (Ogoh *et al.*, 2003) or lower body negative pressure (Murray *et al.*, 1999), while for most patients CO is not related to CVP although there is a relation between CO and diastolic filling of the heart as indicated by echocardiography (Thys et al., 1987).

In order to limit the blood loss during surgery, a strategy of keeping CVP low has been suggested and studies on liver resection patients show a reduction in the blood loss, in morbidity, as in the hospital stay when the intraoperative CVP is kept < 5 mmHg (Jones et al., 1998;Chen et al., 2000). Implementing the same strategy to OLT, one study found that a low CVP increased morbidity as expressed as postoperative renal failure and mortality (Schroeder et al., 2004), while an other study came to the opposite conclusion (Massicotte et al., 2006). We hold it that volume therapy during OLT is better detected by flow related parameters than by vascular pressure(s) (Bundgaard-Nielsen *et al.*, 2007a;Jenstrup *et al.*, 1995;Ejlersen *et al.*, 1995b).

A PAC allows for monitoring pulmonary artery (mean) pressure (PAMP) as well as wedge pressure (PAWP). These values are relevant to patients undergoing OLT since some patients develop both portal and pulmonary hypertension (Krenn & De Wolf, 2008). It remains, however, elusive whether monitoring of PAWP provides advantages over the continuous recording of PAMP. At least it should be considered that a determination of PAWP carries the risk of rupturing a branch of the pulmonal artery and that is likely to be fatal.

Fig. 5. Pulmonary artery mean pressure (PAMP) (±SD and 5th and 95th percentile) and cardiac output (CO) (±SD) for 33 candidates for OLT at rest and during exercise (P. Nissen, unpublished)

A PAMP limit of 30 mmHg may be considered to indicate pulmonary hypertension, but it should be taken into account that there is a direct relationship between PAMP and CO as illustrated during physical exercise (Tolle *et al.*, 2008) and that is also the case for patients under evaluation for OLT (Fig. 5).

If a candidate OLT patient presents a high PAMP, it should accordingly be considered whether the high pulmonary pressure is because of a large CO and thereby unrelated to pulmonary disease. As for other patient categories, it seems more important that the heart is able to generate a reasonable CO than at what pressures it operates. For example, a successful OLT is reported for a patient with a PAMP of 44 mmHg and a CO of 5.7 l/min and with an ability to increase CO to 10 l/min (at a PAMP of 51 mmHg during reperfusion of the liver) (Liu *et al.*, 1996). Similarly, there is even for patients without pulmonary hypertension an often impressive increase in PAMP concomitant with the increase in CO during reperfusion of the grafted liver (Table 1). Furthermore hypoxia leads to pulmonary hypertension of relevance for OLT patients with associated significant pulmonary shunt and at least in case of hypoxia, pulmonary hypertension seems to be related to the patient's iron status (Smith *et al.*, 2008). Accordingly, the iron status of the OLT candidate with pulmonary hypertension and hypoxia should be checked.
