**1. Introduction**

358 Liver Transplantation – Basic Issues

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central pontine myelinolysis following living donor liver transplantation: report of

Orthotopic liver transplantation (OLT) became a treatment modality in Denver (Starzl *et al.*, 1963) and Cambridge, England in 1968 (Calne, 2008) although exposing critically ill patients to extensive surgery was a challenge and in the 1970s, the one year survival rate remained in the vicinity of only 25% (Starzl *et al.*, 1981). One problem was to manage the often impressive blood loss and rapid infusion devices were developed to provide large amounts of blood products at body temperature (Stammers *et al.*, 2005). During OLT the blood loss has, fortunately, declined and in the 1980s, the average number of blood units administered was reduced to 20 and in some centres, ~ 80% of patients are now without a need for administration of blood (Massicotte *et al.*, 2004). Yet, there remains differences among centres and for a number of patients, OLT is associated with a significant blood loss (Massicotte *et al.*, 2004). Furthermore, haemodynamic challenges are inevitable during the operation. Corresponding to the metabolic activity of the liver, the hepatectomy is likely to reduce cardiac output (CO) and in cases for which caval and portal clamping are used, blood accumulates in the splanchnic region and in the lower part of the body which together leads to a decline in CO by 40%-50% (Ozier & Klinck, 2008). Conversely, CO often doubles during reperfusion of the grafted liver as peripheral vasodilatation is provoked by the release of blood from the splanchnic region mixed with the chilled outflow from the liver, potentially with a high potassium concentration (Ozier & Klinck, 2008). Also it may be that the heart is unable to respond with an adequate increase in CO to reperfusion of the grafted liver, or that there is a reduction in CO despite an, apparently, adequate central blood volume (CBV), accepting that reperfusion of the liver and re-establishing splanchnic blood flow may release some cardio-inhibiting factor (Jordan *et al.*, 1999). Given redistribution of the blood volume during OLT, monitoring of the circulation is, ideally, directed to secure CBV rather than the total blood volume.

As for other types of surgery, there is no universally accepted strategy for haemodynamic monitoring during OLT, save a mandatory arterial line and recording of heart rate (HR) by ECG (Ozier & Klinck, 2008). Yet, mean arterial pressure (MAP) and HR are inadequate for monitoring CBV (Bundgaard-Nielsen *et al.*, 2007a). For example, there may be no significant deviations in these variables until a hypovolaemic shock is provoked (Murrell *et al.*, 2009). Furthermore during surgery, HR and especially MAP are affected by the anaesthetic agents and by the surgical stress (Ejlersen *et al.*, 1995a). Despite these limitations in the use of HR and MAP to detect deviations in CBV, the capability to balance CBV is of importance for tissue perfusion and oxygenation and notably for oxygenation of the brain (ScO2) (Nissen *et al.*, 2009a), indicating that advanced cardiovascular monitoring is required to secure the well-being of the patient (Yao *et al.*, 2004;Bundgaard-Nielsen *et al.*, 2007a;Murkin *et al.*, 2007)

In order to maintain CBV during surgery, it is important that normovolaemia is defined. For supine humans the heart operates on the upper flat part of the Frank-Starling curve (Harms *et al.*, 2003) and to establish and to maintain a maximal resting stroke volume for the heart (or CO) secures that the patient remains normovolaemic during the operation and that fluid administration strategy reduces postoperative complications to an extent that affects the hospital stay (Bundgaard-Nielsen *et al.*, 2007a). Such goal directed fluid therapy was introduced by Shoemaker et al. (Shoemaker, 1972;Shoemaker *et al.*, 1988) in regard to CO but without taking the individual and partly genetically determined differences in CO (Snyder *et al.*, 2006) into account. Accordingly, this chapter focuses on how normovolaemia can be established and maintained during OLT despite the difficulties confronting the definition of normovolaemia by the spontaneous changes in stroke volume, CO and (mixed) venous oxygen saturation (SvO2) during the different phases of the operation. A second goal of this chapter is to introduce devices that can be applied for intraoperative monitoring of CBV and ScO2. Focus is on the importance of maintaining a normal CBV to secure cerebral blood flow (CBF) and ScO2 since these variables are taken to express the integrity of the cardiovascular system and their defence, at least potentially, prevents postoperative complications and cognitive dysfunction (Murkin *et al.*, 2007). In addition, the volume administration strategy applied during the operation is addressed.
