**3. Conduct of anaesthesia**

Despite recent advances, liver transplantation remains a major challenge to the anaesthetist due to the important cardiovascular changes throughout surgery: important changes in preload, afterload, arrhythmias, hypotension and hyperkalaemic events. All these increase the chances of severe cardiac dysfunction.

**Temperature***:* central temperature is the blood temperature which bathes the vital organs (heart and brain). Important sites of measurement are the following: tympanic membrane,

Anesthesia for Liver Transplantation http://dx.doi.org/10.5772/intechopen.75167 215

Patients with chronic liver disease usually present many other systemic complications including portal hypertension, ascites, coagulopathy, hyperdynamic circulatory syndrome (high cardiac index and low systemic vascular resistance) and cirrhotic cardiomyopathy. Due to all these changes, advanced haemodynamic monitoring is necessary. Monitoring parameters

Invasive arterial pressure monitoring represents standard practice during liver transplantation. The arterial catheter is usually inserted in the radial artery and is being used for continuous pressure monitoring, blood gas analysis and other blood tests. Due to variations of radial artery pressure which may sometimes underestimate aortic pressure in hypotensive states, when high dose vasopressors are used and after reperfusion of the liver, some anaesthetists prefer using the femoral artery. Despite all these, the mean central and peripheral arterial pressures are usually the same [22]. An important problem when deciding the sites for catheter insertion is the cirrhotic coagulopathy which can lead to important puncture site bleeding. The number and sites of line insertion vary according to the transplant centre and experience.

Central venous pressure (CVP) monitoring is essential during liver transplantation. Central venous pressure is measured via a central catheter inserted in the superior vena cava system. Maintaining a low CVP in a normovolaemic patient can reduce the risk of bleeding but can increase the risk of vital organ hypoperfusion in case of a hypovolaemic patient or a massive

Since its discovery, the pulmonary artery flotation catheter (Swan Ganz) has been considered the gold standard for cardiac output measurement. Swan Ganz catheters are still used routinely in some transplant centres around the world. A pulmonary artery catheter is manda-

Pulmonary artery pressures, cardiac output measurements and mixed venous oxygen saturation help in the diagnosis and management of haemodynamic instability during surgery. The new modified Swan Ganz catheters help anaesthetists with continuous cardiac output measurements and right ventricular end-diastolic volume as a more accurate parameter of

Despite the massive use in the last 40 years, its high cost and patient safety have led to ques-

nasopharynx, distal oesophagus, blood, urinary bladder and rectum [20].

*3.1.2. Haemodynamic monitoring*

*3.1.2.1. Invasive blood pressure*

*3.1.2.2. Central venous pressure*

*3.1.2.3. Cardiac output and pulmonary artery pressures*

tory if pulmonary hypertension is diagnosed or suspected.

bleeding [23].

preload.

tion its utility [24].

and normal values are shown in **Table 1** [21].

Liver transplantation is characterized by haemodynamic instability and various complications that can arise throughout the three important surgical phases: preanhepatic, anhepatic and neohepatic.


#### **3.1. Patient monitoring during liver transplantation**

Liver transplantation is performed under general anaesthesia, and the anaesthetic monitoring plays an important part in a successful liver transplantation as it can expose problems before irreversible damage occurs.

Haemodynamic instability is common during liver transplantation, and that is why the anaesthetic monitoring is complex, being divided into standard monitoring, haemodynamic (invasive and non-invasive), neurologic and neuromuscular monitoring.

#### *3.1.1. Standard monitoring*

According to the American Society of Anaesthesia (ASA) protocols, standard monitoring applies to all patients during all types of anaesthesia with the aim of increasing patients' quality of care. Trained personnel must be present in the operating room during the entire surgery, while continuous monitoring of the oxygenation, ventilation, circulation and temperature is mandatory [19].

**Oxygenation***:* gas monitoring as the level of inspired oxygen (FiO<sup>2</sup> ) and the level of expired CO<sup>2</sup> (ETCO<sup>2</sup> capnography) and blood oxygenation in a continuous form as peripheral capillary oxygen saturation (SpO<sup>2</sup> pulsoxymetry).

**Ventilation***:* chest movements and lung auscultation but also the volume of expired gas and capnography.

**Circulation:** continuous electrocardiogram (ECG) for rhythm, frequency, signs of ischaemia (ST segment), QT interval and measurement of blood pressure in a non-invasive way before induction of anaesthesia.

**Temperature***:* central temperature is the blood temperature which bathes the vital organs (heart and brain). Important sites of measurement are the following: tympanic membrane, nasopharynx, distal oesophagus, blood, urinary bladder and rectum [20].

#### *3.1.2. Haemodynamic monitoring*

**3. Conduct of anaesthesia**

214 Organ Donation and Transplantation - Current Status and Future Challenges

chances of severe cardiac dysfunction.

and neohepatic.

Despite recent advances, liver transplantation remains a major challenge to the anaesthetist due to the important cardiovascular changes throughout surgery: important changes in preload, afterload, arrhythmias, hypotension and hyperkalaemic events. All these increase the

Liver transplantation is characterized by haemodynamic instability and various complications that can arise throughout the three important surgical phases: preanhepatic, anhepatic

• Preanhepatic: dissection and liver mobilization takes place; usually massive bleeding can

• Anhepatic: between clamping hepatic inflow and before graft reperfusion; consists of clamping of the inferior vena cava (IVC); significant decrease in cardiac output (CO) occurs. • Neohepatic: characterized by liver reperfusion, reappearance of flow in the vena cava and vena porta, blood volume goes back to normal; can be complicated by reperfusion syn-

Liver transplantation is performed under general anaesthesia, and the anaesthetic monitoring plays an important part in a successful liver transplantation as it can expose problems before

Haemodynamic instability is common during liver transplantation, and that is why the anaesthetic monitoring is complex, being divided into standard monitoring, haemodynamic (inva-

According to the American Society of Anaesthesia (ASA) protocols, standard monitoring applies to all patients during all types of anaesthesia with the aim of increasing patients' quality of care. Trained personnel must be present in the operating room during the entire surgery, while continuous monitoring of the oxygenation, ventilation, circulation and tem-

**Ventilation***:* chest movements and lung auscultation but also the volume of expired gas and

**Circulation:** continuous electrocardiogram (ECG) for rhythm, frequency, signs of ischaemia (ST segment), QT interval and measurement of blood pressure in a non-invasive way before

capnography) and blood oxygenation in a continuous form as peripheral capil-

) and the level of expired

drome or bleeding from vascular anastomosis (hepatic artery, portal vein).

occur that can lead to hypovolaemia and haemorrhagic shock.

sive and non-invasive), neurologic and neuromuscular monitoring.

**Oxygenation***:* gas monitoring as the level of inspired oxygen (FiO<sup>2</sup>

pulsoxymetry).

**3.1. Patient monitoring during liver transplantation**

irreversible damage occurs.

*3.1.1. Standard monitoring*

perature is mandatory [19].

(ETCO<sup>2</sup>

capnography.

lary oxygen saturation (SpO<sup>2</sup>

induction of anaesthesia.

CO<sup>2</sup>

Patients with chronic liver disease usually present many other systemic complications including portal hypertension, ascites, coagulopathy, hyperdynamic circulatory syndrome (high cardiac index and low systemic vascular resistance) and cirrhotic cardiomyopathy. Due to all these changes, advanced haemodynamic monitoring is necessary. Monitoring parameters and normal values are shown in **Table 1** [21].

#### *3.1.2.1. Invasive blood pressure*

Invasive arterial pressure monitoring represents standard practice during liver transplantation. The arterial catheter is usually inserted in the radial artery and is being used for continuous pressure monitoring, blood gas analysis and other blood tests. Due to variations of radial artery pressure which may sometimes underestimate aortic pressure in hypotensive states, when high dose vasopressors are used and after reperfusion of the liver, some anaesthetists prefer using the femoral artery. Despite all these, the mean central and peripheral arterial pressures are usually the same [22]. An important problem when deciding the sites for catheter insertion is the cirrhotic coagulopathy which can lead to important puncture site bleeding. The number and sites of line insertion vary according to the transplant centre and experience.

#### *3.1.2.2. Central venous pressure*

Central venous pressure (CVP) monitoring is essential during liver transplantation. Central venous pressure is measured via a central catheter inserted in the superior vena cava system. Maintaining a low CVP in a normovolaemic patient can reduce the risk of bleeding but can increase the risk of vital organ hypoperfusion in case of a hypovolaemic patient or a massive bleeding [23].

#### *3.1.2.3. Cardiac output and pulmonary artery pressures*

Since its discovery, the pulmonary artery flotation catheter (Swan Ganz) has been considered the gold standard for cardiac output measurement. Swan Ganz catheters are still used routinely in some transplant centres around the world. A pulmonary artery catheter is mandatory if pulmonary hypertension is diagnosed or suspected.

Pulmonary artery pressures, cardiac output measurements and mixed venous oxygen saturation help in the diagnosis and management of haemodynamic instability during surgery. The new modified Swan Ganz catheters help anaesthetists with continuous cardiac output measurements and right ventricular end-diastolic volume as a more accurate parameter of preload.

Despite the massive use in the last 40 years, its high cost and patient safety have led to question its utility [24].


*3.1.2.4. Other ways of measuring cardiac output*

thetized and intubated patient [26].

60 in an anaesthetized patient [27].

• Oxygen saturation in the jugular bulb (SjvO<sup>2</sup>

• Transcerebral cranial oximetry: resembles SjvO<sup>2</sup>

above 75% show cerebral hyperaemia.

cerebral activity during anaesthesia.

*3.1.4. Neuromuscular monitoring*

*3.1.3. Neurologic monitoring*

cerebral death.

diac cycle; rarely used in liver transplantation.

frequent calibration via thermodilution technique:

The pulse contour analysis is useful for continuous monitoring of cardiac output and needs

• PiCCO system (Pulse-induced Contour Cardiac Output): this consists of a thermistor catheter placed in the femoral artery and can estimate stroke volume. A central venous catheter inserted in the superior vena cava circulation is needed for the pulmonary calibration which must be done every 8 h in a haemodynamic stable patient and more frequent for unstable patients [25].

• LiDCO: it uses the same algorithm for stroke volume monitoring. Lithium chloride is used

• Transoesophageal echocardiography gives continuous information on ventricular function and volume status and allows immediate diagnosis of air or thrombus embolization. It also provides information regarding contractility, valvular function, pericardial or pleural effusion. Its main advantage is the ease of continuous use during surgery due to the anaes-

• Thoracic bioimpedance: it estimates cardiac output and other haemodynamic parameters based on the electric properties of the thorax produced by blood movements during car-

• Bispectral index: Fourier analysis of a fronto-parietal electroencephalogram (EEG). It varies between 0 (coma) and 10 (normal cortical activity) with an adequate value between 40 and

• Transcranial Doppler echography can diagnose vasospasm, intracranial hypertension and

saturation via a central catheter inserted in the internal jugular vein that shows the balance between oxygen intake and consumption. Values below 50% show ischaemia while values

• Electroencephalogram: rarely used for continuous monitoring during surgery; requires a trained anaesthetist who must differentiate pathological changes from normal changes in a

Residual neuromuscular block after the use of neuromuscular blockade agents can have a detrimental effect in patients after surgery causing inadequate hypoxic ventilatory response, depressed pharyngeal tonus leading to an increased risk of airway obstruction and death.

.

): continuous monitoring of venous oxygen

Anesthesia for Liver Transplantation http://dx.doi.org/10.5772/intechopen.75167 217

for transpulmonary calibration and can be injected into a peripheral vein.

**Table 1.** Haemodynamic parameters.

### *3.1.2.4. Other ways of measuring cardiac output*

**Parameter Abbreviation Formula Normal value** Median arterial pressure MAP SBP+(2 × DBP)/3 75–105 mmHg

Stroke volume SV CO/HR × 1000 60–100 ml/beat Stroke volume index SVI CI/HR × 1000 33–47 ml/m2

Cardiac output CO HR × SV/1000 4–8 l/min Cardiac index CI CO/BSA 2.5–4 l/min/m2 Central venous pressure CVP Measurement 2–6 mmHg Central venous oxygen saturation ScvO<sup>2</sup> Measurement 70–80%

Extravascular lung water index EVLWI EVLW/PBW 0–7 ml/kgc Global ejection fraction GEF SV × 4/GEDV >20%

Global end-diastolic volume index GEDI CI × MTt × f(S1/S2) 650–800 ml/kgc

Intrathoracic blood volume index ITBI 1.25 × GEDI 850–1000 ml/m<sup>2</sup> Left ventricular stroke work LVSW SI × MAP×0.0144 8–10 g/m<sup>2</sup>

Left ventricular stroke work index LVSWI SVI× (MAP-PAOP) × 0.0136 50–62 g/m<sup>2</sup>

Mean pulmonary artery pressure MPAP PASP+(2 × PADP)/3 9–18 mmHg Oxygen consumption VO<sup>2</sup> C(a-v)O<sup>2</sup> × CO × 10 200–250 ml/min Oxygen delivery DO<sup>2</sup> CaO<sup>2</sup> × CO × 10 950–1150 ml/min Pulmonary artery occlusion pressure PAOP Measurement 6–12 mmHg Pulmonary artery systolic pressure PASP Measurement 15–30 mmHg Pulmonary artery diastolic pressure PADP Measurement 8–15 mmHg Pulmonary vascular resistance PVR 80× (MPAP-PAOP)/CO <250 dynes/s/cm<sup>5</sup> Pulmonary vascular resistance index PVRI 80× (MPAP-PAOP)/CI 255–285 dynes/s/

Stroke volume variation SVV SVmax-SVmin/SVmean×100 10–15%

Systemic vascular resistance SVR 80× (MAP-RAP)/CO 800–1200 dynes/s/

Systemic vascular resistance index SVRI 80× (MAP-RAP)/CI 1970–2390 dynes/

) + 0.003 × PaO<sup>2</sup> 16–22 ml/dl

/beat

/beat

cm5 /m2

cm5

sec/cm5/m2

/beat

) + 0.003 × PvO<sup>2</sup> 15 ml/dl


SpO<sup>2</sup> Measurement 95–100%

Arterial oxygen concentration CaO<sup>2</sup> (0.0138 × Hb × SaO<sup>2</sup>

216 Organ Donation and Transplantation - Current Status and Future Challenges

Venous oxygen concentration CvO<sup>2</sup> (0.0138 × Hb × SvO<sup>2</sup>

Extravascular lung water EVLW CO × DSt-0.25GEDV

Global end-diastolic volume GEDV CO × MTt × f(S1/S2)

Intrathoracic blood volume ITBV 1.25 × GEDV

**Table 1.** Haemodynamic parameters.

Arteriovenous oxygen difference C(a-v)O<sup>2</sup> CaO<sup>2</sup>

Peripheral capillary oxygen

saturation

The pulse contour analysis is useful for continuous monitoring of cardiac output and needs frequent calibration via thermodilution technique:


#### *3.1.3. Neurologic monitoring*


#### *3.1.4. Neuromuscular monitoring*

Residual neuromuscular block after the use of neuromuscular blockade agents can have a detrimental effect in patients after surgery causing inadequate hypoxic ventilatory response, depressed pharyngeal tonus leading to an increased risk of airway obstruction and death. Peripheral nerve stimulation and depth of block can be assessed using single twitch, train of four, tetanic stimulation and double burst stimulation.

• Preanhepatic phase: cirrhotic patients usually have variate quantities of ascites; the anaesthetist must try and compensate it in order to reach normovolaemia and avoid hypovolaemia during the next phase (anhepatic) when clamping the inferior vena cava. Albumin of

Anesthesia for Liver Transplantation http://dx.doi.org/10.5772/intechopen.75167 219

• Anhepatic phase: fluid restriction is the best solution in this phase while maintaining adequate arterial pressure with the help of vasopressors. The vasopressor of choice is noradrenaline, and the parameters measured with the PiCCO system can guide us to using

• Neohepatic phase: in this stage, the patient needs adequate volemic resuscitation guided

Albumin determines the oncotic pressure that keeps fluids in the intravascular space. Cirrhotic patients usually have low albumin levels [32]. Studies have shown that the use of albumin during liver transplantation decreases the amount of intraoperative fluids used and the frequency of pulmonary oedema in cardiac and noncardiac surgery [33]. It has also been proved that albumin decreases mortality in cirrhotic patients, decreases the incidence of post-

The use of Hetastarch is not recommended as it affects platelet aggregability and increases the risk of bleeding by decreasing the concentration of coagulation factor 8 [33]. Gelatines can have numerous side effects: anaphylactic reactions, a decrease in thrombin generation and

Manitol can be used in the anhepatic phase before clamping of the IVC (0.5 g/kgc) in order to

PiCCO monitoring has a number of advantages: accurate CO calculations and guiding fluid management. ITBV is an accurate parameter of preload even when IVC is clamped [37]. We

Fluid management is done using PiCCO parameters determined during the three phases of the liver transplantation. This guidance of fluid therapy decreases the post-anaesthesia care unit stay and mortality [39]. The decisional tree regarding fluid management is presented in **Table 2**.

TOE can also be helpful in high-risk patients with various cardiac problems. It has the advantage of direct assessment of cardiac contractility and assesses response to inotropes and vole-

The use of different monitoring techniques is the key to successful management of haemody-

There are a variety of substances that can be used when haemodynamic instability takes place during liver transplantation. Noradrenaline is most often used, followed by adrenaline and

by the PiCCO parameters; an important decrease in vasopressors takes place.

reperfusion syndrome and the use of vasopressor agents [34].

can also use SVV in order to predict fluid responsiveness [38].

namic instability and fluid guidance during liver transplantation.

*3.2.2. Vasoactive substances and inotropes*

dobutamine. Indications are shown in **Table 3**.

worsening of fibrinolysis which is specific in the anhepatic phase [35].

avoid blood congestion in the liver and intraabdominal organ oedema [36].

mic status. It can diagnose embolic complications and cardiac tamponade [40].

20 or 5% is used for volemic resuscitation.

inotopes such as dobutamine.

#### *3.1.5. Other parameters monitored during liver transplantation*

Other parameters monitored during liver transplantation include the following:


#### **3.2. Haemodynamic management during the three phases of liver transplantation**

#### *3.2.1. Volemic resuscitation*

Ever since the first successful liver transplantation in 1960, the surgery has been associated with significant bleeding and an increased amount of blood products transfused [28]. Blood products used during liver transplantation have declined significantly in the last 20 years. Even if bleeding risk has decreased over time, it still can induce a volemic stress.

Clamping of the inferior vena cava during the second phase (anhepatic) of the liver transplantation leads to an important decrease in preload, CO and arterial pressure which need a quick diagnosis and management. Normal response of right ventricle (RV) and left ventricle (LV) to stress does not take place due to all the substances released from the liver in the anhepatic phase.

Continuous assessment of patient's volemic status and the amount of perfused fluids represent the key to a successful liver transplantation. This can be done using dynamic measurements of CVP and pulmonary capillary wedge pressure (PCWP), but these parameters do not correlate with changes in CO [29]. Another way of assessing fluid responsiveness is the use of stroke volume variation (SVV) and global end-diastolic volume index (GEDI). Inadequate fluid therapy can lead to pulmonary oedema, abnormal gas exchange, congestion, a decrease in perfusion and oedema of the graft [30].

This study does not offer an answer for the ideal monitoring system and guiding of fluid therapy [31]. In our clinic, the guidance of fluid management is done with the pulmonary thermodilution technique and pulse contour wave analysis via the PiCCO system.

Using adequate vasoactive substances, which protect the brain, heart and kidney, led to a greater haemodynamic stability, adequate CO and renal perfusion [31]. The CVP can also be correlated with the severity of the post-reperfusion syndrome [32].

Specific fluid management during liver transplantation can be described according to the three surgical phases:


Albumin determines the oncotic pressure that keeps fluids in the intravascular space. Cirrhotic patients usually have low albumin levels [32]. Studies have shown that the use of albumin during liver transplantation decreases the amount of intraoperative fluids used and the frequency of pulmonary oedema in cardiac and noncardiac surgery [33]. It has also been proved that albumin decreases mortality in cirrhotic patients, decreases the incidence of postreperfusion syndrome and the use of vasopressor agents [34].

The use of Hetastarch is not recommended as it affects platelet aggregability and increases the risk of bleeding by decreasing the concentration of coagulation factor 8 [33]. Gelatines can have numerous side effects: anaphylactic reactions, a decrease in thrombin generation and worsening of fibrinolysis which is specific in the anhepatic phase [35].

Manitol can be used in the anhepatic phase before clamping of the IVC (0.5 g/kgc) in order to avoid blood congestion in the liver and intraabdominal organ oedema [36].

PiCCO monitoring has a number of advantages: accurate CO calculations and guiding fluid management. ITBV is an accurate parameter of preload even when IVC is clamped [37]. We can also use SVV in order to predict fluid responsiveness [38].

Fluid management is done using PiCCO parameters determined during the three phases of the liver transplantation. This guidance of fluid therapy decreases the post-anaesthesia care unit stay and mortality [39]. The decisional tree regarding fluid management is presented in **Table 2**.

TOE can also be helpful in high-risk patients with various cardiac problems. It has the advantage of direct assessment of cardiac contractility and assesses response to inotropes and volemic status. It can diagnose embolic complications and cardiac tamponade [40].

The use of different monitoring techniques is the key to successful management of haemodynamic instability and fluid guidance during liver transplantation.
