Number of patients
Percentage (%)
Malignant pathologies
• Colon metastasis
• Neuroendocrine metastasis
• Metastasis of another origin
• Hepatocellular carcinoma
• Colangiocarcinoma
• Vesicular cancer
• Others
826
552
22
31
88
22
18
93
85.86
61
2.9
4
11.5
2.9
2.3
12
Benign pathologies
• Hemangiomas
• Live related donor
• Adenomas
• Focal nodular hyperplasia
• Hydatid cyst
• Others
136
36
35
23
21
8
13
14.14
26.5
26
17
15.5
5.9
9.5
Anatomy and Hepatic Physiology
It is vital for the anaesthesiologist carrying out perioperative care in hepatectomies to know the anatomy and physiology of the liver.
It is in these concepts that we shall find the bases for reducing haemorrhages and the way towards preventing the increase of cellular injury during the surgical ischemia periods.
Anatomic and Physiological Characteristics of the Liver with Surgical and Anaesthetic Relevance
The liver is the largest solid organ in the body, and weighs about 1.5 kg in an adult. It is placed in the right quadrant of the abdomen and is divided into four lobes: right, left, quadrate lobe, and caudate lobe.
At the same time, the right and left lobes are divided into segments which are defined by the distribution of arterial vessels and the biliary tree.
In the year 2000 in the city of Brisbane, a meeting of specialists was held with the objective of creating a definitive nomenclature to describe the different procedures on the liver. In subsequent years, this nomenclature has been adopted worldwide, and it is currently the most widely accepted one [8].
Hepatic surgery can be carried out according to lobe and segment distribution or disregarding this division.
Thus, the resection of a hepatic lobe will be called hemihepatectomy or right or left hepatectomy (Figs. 10.1 and 10.2).
Fig. 10.1
Hepatic tumor
Fig. 10.2
Intraoperative photo of a right hepatectomy
At the same time, the resection of a single segment is called segmentectomy and when it involves two segments, bisegmentectomy.
The most important hepatic surgery involves the removal of the right or left lobe as well as one or two contralateral segments. This surgery is called hepatic trisegmentectomy [8].
Finally we call it an atypical hepatic resection when the cut on the hepatic tissue does not respect segmentary distribution.
It is important to bear in mind that this organ receives double circulation through the contribution of the portal vein and the hepatic artery. The latter, narrower, is responsible for between 25 and 30% of the hepatic flow but 60% of the oxygen available for this organ. The portal vein contributes 70% of the hepatic flow and 40% of the total oxygen [9].
The portal vein branches ramify within the liver, and their division accompanies the hepatic sinusoids. Portal blood goes through these sinusoids and is collected by the centrilobular vein.
The hepatic artery branches run along the portal vein and finally transform into arterioles, pre-capillaries, and capillaries. Arterioles have sphincters which are part of the hepatic flow regulation [9].
After going through the hepatic sinusoids, blood coming from arterial and portal circulation is collected by three hepatic veins which drain their content into the vena cava [10].
Under normal circumstances, the liver extracts only 40% of the total oxygen delivered, but in patients under surgery or anaesthesia or suffering from diseases such as cirrhosis, the demand for oxygen may increase [9].
Hepatic flow represents about 25% of the total minute volume, which equals the delivery of about 1,500–1,800 ml of blood per minute [10].
There is a close relationship between the portal vein flow and the hepatic artery. When portal flow decreases, the hepatic artery complements it by increasing its flow [10].
While portal blood flow remains stable, the hepatic artery maintains an intrinsic self regulation system which keeps its volume constant in spite of the systemic pressure variations [11, 12].
Maintaining a stable blood flow towards this organ, under different hemodynamic conditions, is accounted for given the need to support the metabolism of endogenous and exogenous substances, even in critical clinical cases [9, 11, 12].
In other words, hepatic metabolism depends on the blood flow received in the time unit and only stops under extreme circumstances.
Hepatic irrigation is, therefore, an exception system, since it functionally does not respond to the same factors that lead to vasoconstriction or vasodilatation in the rest of the vascular tree.
The effects of the acid base or the concentration of oxygen only alter the diameter of the hepatic arterioles when they reach marginal conditions. Self-regulation would be controlled based on a neural type mechanism [13].
We should also mention, though with a lesser influence on this system:
Cyclical alterations corresponding to spontaneous ventilation.
Intrahepatic osmolarity.
Excessive use of positive end-expiratory pressure (PEEP).
Hypocapnia and hypercapnia.
Surgery: surgery itself diminishes hepatic flow. Superior abdominal surgeries are those with the largest influence
Anaesthesia: inhalatory anaesthetics decrease hepatic flow, although the most modern ones seem to do so in lower quantities (sevorane) and even increase it (isofluorane).
Intravenous anaesthetics do not appear to have any influence over hepatic flow.
Hepatic Endothelium and Influence on Central Venous Pressure
The vascular endothelial cells in the hepatic sinusoid (mainly those corresponding to the portal vein branches), have fenestrations of a diameter which varies between 100 and 500 nm, and are not supported on any basal membrane.
The importance of these fenestrations lies in that they place the blood perfused to the liver in direct contact with the hepatic interstice. In other words, there is no defence against the changes in hydrostatic pressure [9, 10].
The larger orifices are found in the centrilobular region. These can change their size as a response to intravascular pressures, the action of vasoactive drugs, and the presence of toxins [12].
As incoming blood is controlled by a self-regulating system, there is no possibility for the liver to receive excessive flow that would unproportionally increase the internal volume.
The only way of doing this is through the increase of the central venous pressure which exercises a retrograde strength on the vena cava and the suprahepatic vein. The increase of the central venous pressure successively leads to the increase of the hepatic volume, the increase in the filtration of liquids towards the interstice, a higher lymphatic flow, and finally to the formation of ascitic liquid [9].
The arterioles contract and ease the passage of liquids towards the interstice as a response to the higher central venous pressure.
However, thanks to the lymphatic system which can drain great volumes, there is no accumulation of interstitial fluid in the liver.
Lymphatic vessels have the ability of increasing the density of proteins in their interior. These increase until they reach plasmatic concentration. Thus, oncotic pressures are matched and the interstice does not become a fluid deposit. Additionally, the liver surface can exude liquid, thus ejecting its excess [9–11].
Before reaching this extreme situation, the liver becomes a fabulous blood reservoir due to the increase in its internal volume.
Carrying out a liver resection under these circumstances implies the real possibility of increasing the risk of provoking a significant haemorrhage during surgery.
Surgical Manoeuvres that Diminish Intraoperative Bleeding
Pringle Manoeuvre (PM)
First described by Pringle in 1908, it has proven effective in decreasing haemorrhage during the resection of the liver tissue [14]. It is frequently used, and it consists in temporarily occluding the hepatic artery and the portal vein, thus limiting the flow of blood into the liver, although this also results in an increased venous pressure in the mesenteric territory [15] (Fig. 10.3).
Fig. 10.3
Surgical maneuvers liver vascular occlusion
Hemodynamic repercussion during the PM is rare because it only diminishes the venous return in 15% of cases. The cardiovascular system slightly increases the systemic vascular resistance as a compensatory response, thereby limiting the drop in the arterial pressure. Through the administration of crystalloids, it is possible to maintain hemodynamic stability [16, 17].
In the 1990s, the PM was used continuously for 45 min and even up to an hour because the depth of the potential damage that could occur due to hepatic ischemia was not yet known [14].
During the PM, the lack of oxygen affects all liver cells, especially Kupffer cells which represent the largest fixed macrophage mass. When these cells are deprived of oxygen, they are an endless source of production of the tumour necrosis factor (TNF) and interleukins 1, 6, 8 and 10. IL 6 has been described as the cytokine that best correlates to postoperative complications [15, 17–19].
In order to mitigate the effects of continuous PM, intermittent clamping of the portal pedicle has been developed. This consists of occluding the pedicle for 15 min, removing the clamps for 5 min, and then starting the manoeuvre again.
Total Vascular Exclusion (TVE)
This was described by Heaney and collaborators and initially associated to 30% mortality due to its use. As a result of this, it was quickly abandoned and only used again when the development of liver transplant programmes led into greater knowledge of the physiopathology of this surgical manoeuvre [21].
The classic vascular exclusion adds to the occlusion of the hepatic artery and the portal vein, and the clamping of the infrahepatic and the superior vena cava. Thus, we prevent retrograde flow of venous blood (Fig. 10.3).
There are variations of this manoeuvre described, with the intention of mitigating its risks; for example, the occlusion of the suprahepatic veins tributaries of the area to be resected, to avoid the total interruption of the flow of the cava. In these cases, the venous return remains undamaged [22].
Used less frequently than the Pringle manoeuvre, the TVE is useful in the resection of tumours adjacent to large vessels to diminish the risks of massive haemorrhage or air embolism [22].
This modality can also be intermitted, alternating periods of ischemia with periods when circulation is re-established to mitigate possible consequences due to the lack of oxygen [23].
Total occlusion of the vena cava damages the filling pressures of the right cardiac cavities, thus causing a drop in the venous return higher than 50% and, consequently, of the minute volume. Its clinical manifestation is a decrease in systemic arterial pressure, which receives an immediate compensatory response through the increase in the systemic vascular resistance (up to 80%), in an effort to decrease the arterial hypotension [22–24]. The anaesthesiologist can help these compensatory mechanisms through the administration of fluids and the use of vasoactive drugs. The intravenous use of fluids during this period must be carefully managed, since when the clamps are released, there can be saturation in the liver capacity and an increase of the haemorrhage from the exposed surface of the organ.
A persistent hypotension during TVE, in spite of the vasoactive drugs, is the main cause of interruption of the manoeuvre [24, 25].
As with PM, TVE should not be used for prolonged periods of time. The choice of an intermittent method allows for greater use of time [21] (Table 10.2).
Table 10.2
Differences between the Pringle manoeuver and total vascular exclusion
Pringle manoeuver | Total vascular exclusion |
|---|---|
Greater number of transfusions | Greater number of complications |
Greater ischemia/reperfusion effect | Greater hemodynamic instability |
Shorter hospital stay | Technically difficult for the intermittent procedure |
Morbimortality of the TVE has been related in different series studied with the amount of blood transfused, the clamping time, and the histology of the remaining liver [23].
Anaesthetic Technique
When an anaesthesiologist is going to take part in a liver resection, he or she should assess the following considerations prior to the surgery: size of the liver resection to be carried out, clinical condition of the patient, preparation for surgery and necessary intraoperative monitoring, possibility of using Fast Track, and the place of post-operative care in the first few hours following surgery (Intensive Care Unit or Anaesthetic Recovery Unit).
Both inhalational anaesthesia and intravenous anaesthesia (total intravenous anaesthesia—TIVA) can be used in all their variations and without restrictions in liver resections. It will only be necessary to avoid those anaesthetics that diminish the hepatic flow, though they are practically out of use nowadays.
Monitoring should be according to the complexity of the surgery and the clinical condition of the patient. Routine monitoring in these types of surgery consists of: dynamic electrocardiography, capnography, oximetry, invasive arterial pressure, and periodic blood tests. Should TIVA be chosen for the anaesthetic technique, BIS is a vital monitor that must be accompanied by an adequate control of muscle relaxation. The control of central temperature and ST segment depression in DII and V5 must also be routine [27].
We should specially mention the central venous pressure (CVP) and its intraoperative control as a parameter highly related to bleeding in patients [28].
Monitoring of the CVP is up to now mandatory, although mini invasive monitoring could replace it in the future. With this method and only by using the invasive arterial pressure can be obtain constant values of systolic volume variation (SVV) or pulse pressure variation (PPV), which provide excellent guidance when restoring the blood [29].
Patients who require a liver resection surgery need at least two venous accesses as large as possible, given the potential need to administer fluids and homoderivatives quickly. Due to the need to measure CVP, one of these venous accesses needs to be central. All venous lines need to be located in the superior vena cava territory (arms and neck), since a vascular exclusion manoeuvre used would limit the desired administration of fluids [27].
Lately, crystalloids are the fluids of choice in high-risk patients, since colloids have been linked to higher renal failure and postoperative mortality [30–32].
Within the group of crystalloids, physiological solution is known for leading to hyperchloremia and acidosis. Both conditions are achieved with little volume, and are clearly damaging in procedures where the metabolic conditions can change quickly [32, 33].
Crystalloids which contain lactate are less criticized, mainly because they can maintain an artificial high level in plasma, which would lead us to conclude that the hyperlactacidemia present is the result of a poor postoperative evolution on the part of the patient [34].
The recommendation regarding the use of crystalloids basically consists of a very balanced solution such as Plasmalyte, whose osmolarity is close to plasmatic, thus contributing more acceptable metabolic results [35].
Nowadays, appropriate anaesthetic technique includes the use of protective mechanic ventilation to prevent pulmonary injury and post-operative complications. Generally speaking, a current volume between 6 and 8 ml/kg is sufficient for effective intraoperative ventilation in patients without prior pulmonary pathologies. The weight used in this equation needs to be ideal for each patient. Constant use of PEEP during mechanical ventilation will prevent pulmonary collapse and very probably the need for pulmonary recruitment with high peaks of positive pressure [36, 37].
Towards the end of the surgery, it is necessary to administer the necessary volume to re establish hemodynamic stability, without the need of pharmacological support or similar to the pre-surgical conditions.
It is desirable not to over-expand patients, among other considerations, because this will help to prevent later complications (e.g., oedemas, anastomosis filtrations).
The anaesthesiologist should have the ability to focus his intraoperative work on keeping the patient in an appropriate balanced metabolic condition which is pain-free and which bears an acceptable level of glycaemia, is normothermic, and has an appropriate concentration of Hb. Additionally, it should be hemodynamically stable, thus ensuring an appropriate consumption of oxygen and a convenient anaesthetic depth with enough muscle relaxation to allow for proper surgical work [38].
Relationship Between Central Venous Pressure (CVP) and Intraoperative Haemorrhage
The relationship between the intraoperative bleeding in liver surgery and CVP was explained in the section where we described the anatomical and physiological dependency between the endothelium, retrograde venous pressure, and intrahepatic blood volume.
Keeping a high CVP implies greater blood loss due to the accumulation of fluids in the liver. On the other hand, when the CVP is low, bleeding will not be a problem, but there might be a higher risk of air embolism [28, 39–43].
It is advisable to keep the CVP below 5 cm of H2O, at the time of resection. During these periods, it will be necessary to use vasoconstrictive drugs such as phenylephrine or norepinephrine to maintain average arterial pressure between 50 and 60 mmHg [44–46] (Fig. 10.4).
Fig. 10.4
Hepatic resection surgery with low central venous pressure. No bleeding is observed in the tissue
Some authors propose replacing the CVP measure for pressure monitoring in a peripheral vein (in the arm) if it is at the same height as the right atrium. These researchers grant peripheral venous pressure (PVP) the same value as CVP because they have found an excellent correlation between the two parameters, with a discordance level of just 4% [47, 48].
In order to achieve a CVP below 5 cm of H2O, it is necessary to impose an intense restriction of the crystalloid infusion from the beginning of the surgery. This measure is frequently not enough on its own, and it is therefore necessary to resort to the administration of drugs in order to achieve the objective set.
The use of venous vasodilators has been described, but the use of diuretics can be a very effective way of obtaining very low levels of CVP without the need of other measures.
Furosemide (0.5 mg/kg), is normally injected in a single dose after obtaining the first basal CVP register at the beginning of the surgery. Its use necessarily implies the serial control of the potassium level in blood during the procedure.
Diuresis, generally speaking, is above 10 ml/kg towards the end of the surgery, which shows the extensive loss of fluids achieved. However, we should note a brief period of interperative oliguria when hypovolaemia is at its highest. Arterial pressure should be maintained through the administration of vasoconstrictive drugs until volemia is recovered at the end of the surgery.
When there is a drop in the effective volemia, the body responds with compensatory mechanisms to maintain constant arterial pressure. In a first phase, the activation of neurohormonal elements takes place which derive flow from the muscle, skin, and splanchnic territory towards vital organs. Up until then, hypovolemia can result in minimal hemodynamic changes.
In more advanced stages, the activation of baroreceptors leads to the release of catecholamines with the subsequent increase in peripheral resistance. This course of action can partially compensate the fall in the venous return and maintain an arterial pressure close to the usual one. Finally, we should add the effect of the renin–angiotensin–aldosterone system, which increases the effect already begun by the sympathetic system [48–50].
The choice of vasoactive drugs to be used during this surgical moment lies within the spectrum of those which ease or even increase mechanisms of compensation. Phenylephrine is the first drug of choice since it behaves lightly and selectively on vascular resistance. A dose of 0.2–0.3 μg/kg/min is first administered, and later increased as necessary. It is unusual to reach a dose of 1 μg/kg/min and, generally, it is not necessary to add other drugs to ensure patients’ hemodynamic stability. When thermodilution catheters have been used under these intraoperative conditions, vascular resistance figures registered have never gone above 1,300 dynas.seg.m2 [51].
Once the hepatic resection period is over, it is necessary to re-establish volemia. Preventing haemorrhages and the absence of transfusions also appears to maintain an adequate immunological level, with considerable improvement in rates of infection. There are hypotheses that even support the possibility of a lower post operative tumoral recurrence [52].
Other Causes that Can Influence Intraoperative Bleeding
Undoubtedly, there are other causes that can strongly influence intraoperative bleeding during a liver reception.
One of them is PEEP, which when increasing transthoracic pressure during a part of the respiratory cycle, increases pressure on the inferior vena cava and its draining territory. There is a notable increase of bleeding if PEEP is maintained during the resection, even with very low CVP [53].
The other situation which can increase the loss of blood from the hepatic surface is Trendelenburg position which undoubtedly increases it, or that of reverse Trendelenburg which decreases it. Both situations can be related to the movement of the blood mass towards one or the other side of the body, according to which one is used [54].
Patients with Preoperative Morbility
The effect of chemotherapeutic drugs on the hepatic tissue does not go unnoticed. Drugs producing the greater organic changes are oxaliplatin, Avastin, and irinotecan, which provoke steatosis, sinusoidal obstruction, and fibrosis [55, 56]. When these patients are later operated on, it is more difficult to diminish the bleeding, even with an adequate reduction of CVP. During the postoperative stage, the changes on the tissue as a result of the chemotherapy increase the possibility of hepatic insufficiency [55]. The theoretical time in which these chemotherapy-associated pathologies diminish their potential to generate greater hepatic damage is 6 weeks after the last treatment [57, 58].
Other Strategies to Diminish Bleeding
Avoiding blood transfusions during any type of surgery is nowadays a mandatory goal for all anesthesiologist doctors. During hepatic resection surgery, haemorrhage is related to the patient’s prior conditions, to the technical difficulty presented by the resection, and also very associated with the anaesthesiologist’s and surgeon’s experience in these procedures [60].
Other strategies have been described in hepatectomies, in addition to the decrease of CVP. These can be used jointly or separately to inhibit haemorrhages.
The anaesthesiologist can continuously administer antifibrinolyctic drugs such as tranexamic acid, although this is not a widely spread practice. It is also possible to use normovolemic hemodilution during surgery with a double objective: to decrease CVP, and to have autologous and fresh blood for the end of the surgery. The latter method has proven to be safe and efficient, especially in live related donors [61]. At many institutions, the use of field blood recovery or cell saver is systematically included when the case calls for it [62].
In the last decade, many anaesthesiologists’ adherence to blood administration procedure guidelines has resulted in the avoidance of unnecessary transfusions in patients undergoing high complexity surgeries.
These guidelines are based on scientific research which show that even with critical patients, a haemoglobin level of 7 g/dl does not increase surgical risk [63]. Hypothermia is another condition that anaesthesiologists know very well, and which they seek to prevent to maintain control of haemostasis.
Body temperature easily drops during hepatic resections, given the wide exposure of abdominal organs, cold fluid lavage, and ventilation with gases at room temperature. Control of hypothermia needs active work from the anaesthesiologist: use of thermal blankets, the administration of intravenous hot liquids, abdominal cavity lavage, and the heating of inspired gases, etc. During the hepatic resection surgery, it is necessary to maintain control of body temperature until the patient recovers consciousness during the immediate post-operative stage [64].
The recombinant factor VII, one of the most promising drugs in the field of haemostasis during the last decade, should be included among the possible therapies to be used in liver resections. In the case of coagulation alterations that lead to severe haemorrhage, factor VII will allow for control of the bleeding and sufficient time to make the necessary haemostasis corrections. Although it has been available for several years, its cost seems to be a limiting factor in is frequent use [65].
Finally, we could mention other techniques in the anaesthesia area which help towards preventing the increase of haemorrhage during hepatic surgery: [66, 67].
Not using heparin, even at very low doses in the arterial line lavage liquids.
During pre-anaesthesia assessment, we should consider if the administration of iron, erythropoietin/eritropoyetina, or vitamin K is necessary according to the patient’s condition.
Study all patients with Von Willebrand disease and prescribe desmopressin when necessary.
Send the patient to the hemotherapy service to begin collection of autologous blood before surgery.
Surgery has also contributed, with sophisticated equipment to allow for bleeding-free hepatectomies. Those most used are ultrasonic scalpel, Argon beam, and haemostatic material with fibrin which can be placed on the liver surface to favour coagulation [66–68].
The angiography with arterial embolisation not only allows for the reduction of tumours before surgery but also helps decrease blood flow towards the anatomic sector where the operation is going to take place. It is an excellent and efficient technique to effectively mitigate intraoperative bleeding [69].
New surgical techniques have also been described to carry out small resections with little loss of tissue and a very low possibility of bleeding [70].
Another widely adopted method for preserving healthy tissue surrounding a malignant process or accessing tumours in difficult areas is radio frequency. It consists of using specially designed needles which are located within the metastasis which is destroyed through intense heat. Radio frequency also has the advantage of allowing the treatment of unresectable tumors through a mini invasive technique [71].
Ultrasound helps the placing of the needle when the use of radio frequency is decided upon [72].
Laparoscopic and robotic techniques have also been adopted to carry out hepatic resections, thus avoiding large incisions, hemorrhages, and a low amount of post-operative pain [73, 74].
Nowadays, hepatic resections at high surgical volume centres is a procedure which carries minimal risk of intraoperative bleeding [75].
Hepatic Injury due to Ischemia: Pre Conditioning
The use of hepatic fluid occlusion manoeuvres to diminish bleeding causes liver injury due to ischemia, and its consequences and prevention are studied by many authors, especially because the objective is to preserve the functions of the remaining liver so that the patient can have a swift and appropriate recovery [76].
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