Liver transplantation

In 1955, Welch performed the first liver transplant in dogs. In 1963, a team of researchers led by Starzl performed the first successful liver transplant in humans.

The number of liver transplants has been steadily increasing, with 3,450 patients being operated on in the United States in 1994. The one-year survival rate after elective liver transplantation in low-risk patients is 90%. Improved results can be attributed to more careful patient selection, improved surgical techniques and postoperative management, and more frequent repeat transplants in cases of rejection. Improved immunosuppressive therapy has also had a positive effect on surgical outcomes.

Liver transplantation is a complex treatment method that does not begin with surgery and does not end with it. Only specialized centers that have all the necessary conditions can perform it.

The patient and his family need psychological and social support. There should be a program for providing donor organs. Survivors need lifelong monitoring by a hepatologist and surgeon and treatment with expensive drugs (immunosuppressants and antibiotics).

Physicians caring for these patients should be in contact with the transplant center. They should be aware of late complications, especially infections, chronic rejection, biliary complications, lymphoproliferative and other malignancies.

It is not surprising that the cost of liver transplantation is high. Technical advances, an increase in the number of transplant teams and the development of cheaper immunosuppressants can reduce the cost of treatment. It should be comparable to the cost of treatment in the last year of life of patients who, due to some circumstances, did not undergo liver transplantation.

Inevitable progression of liver failure leads to the need for transplantation due to the occurrence of serious complications (e.g., gastrointestinal bleeding, encephalopathy, coma, uremia) that threaten the life of the patient. In acute liver failure, intensive care methods allow for the survival of 5-20% of patients. At the same time, the overall one-year survival rate of recipients with orthotopic liver transplantation has reached 80% and above. Long-term survival rates are also quite high with a noticeable improvement in quality of life.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ]

Pathophysiological changes in terminal liver failure

The liver has numerous synthetic and metabolic functions, so the terminal stage of the disease affects almost all organs and systems of the body.

Patients with terminal liver failure are characterized by a picture of the hyperdynamic status of the cardiovascular system with a significant increase in cardiac output, tachycardia, and a decrease in total peripheral vascular resistance. In diseases that destroy normal liver architecture, portal hypertension develops and extensive varicose venous collaterals are formed in the abdominal wall, omentum, retroperitoneal space, and gastrointestinal tract. In addition to the significant danger associated with bleeding from varicose vessels, the extensive network of arteriovenous anastomoses leads to low systemic vascular resistance and high cardiac output.

Patients with cirrhosis usually have varying degrees of oxygenation, transport, and delivery disorders. Intrapulmonary shunting, often seen in patients with terminal liver disease, leads to hypoxemia and is complicated by pleural effusions and bilateral atelectasis with increased IAP due to severe splenomegaly and ascites. Intrapulmonary shunting is the result of increased concentrations of vasodilators (glucagon, vasoactive intestinal polypeptide, ferritin), which play an important role in the development of hypoxemia. Gas retention in the lower lungs and decreased ventilation-perfusion ratio with subsequent hypoxemia often occur. Increased CO and BCC in cirrhosis may secondarily affect the pulmonary vascular bed with subsequent development of pulmonary hypertension.

The pathogenesis of fluid retention in patients with cirrhosis is complex and involves increased secretion of ADH and decreased delivery of filtrate to the efferent segments of the nephron. There are many neural, hemodynamic, and hormonal factors that are important in the pathogenesis of sodium retention in patients with cirrhosis. As the effective volume decreases, sympathetic changes increase, most likely due to stimulation of volume receptors. This is accompanied by increased renin activity, which increases aldosterone secretion via the angiotensin system. Increased sympathetic tone and increased aldosterone activity result in sodium retention in the tubules. The retention is aggravated by redistribution of intrarenal blood flow, which results from both increased vasoconstrictor action of the sympathetic nervous system and activation of the renin-angiotensin system. PG and the kallikrein-kinin system also participate in sodium retention, performing a compensatory or neutralizing role in the functioning and circulation of the kidneys. As soon as further increase in the concentration of these substances ceases, decompensation occurs and renal failure of varying severity develops.

Ascites results from venous hypertension, decreased protein synthesis, and sodium and fluid retention due to a relative excess of aldosterone and vasopressin. Treatment often includes diuretics, which in turn may cause electrolyte and acid-base disturbances and decreased intravascular volume. However, diuretic therapy is often accompanied by many complications, such as hypovolemia, azotemia, and sometimes hyponatremia and encephalopathy. Hypokalemia observed in cirrhosis may be caused by inadequate diet, hyperaldosteronemia, and diuretic therapy. It is clear that diuretic therapy without proper volume control may reduce the effective plasma volume with subsequent renal decompensation and hepatorenal syndrome.

Hepatorenal syndrome usually develops in patients with classic symptoms of liver cirrhosis, portal hypertension, and especially ascites. These patients usually have normal urine output, but the urine, even concentrated, contains almost no sodium, and the levels of creatinine and urea in the blood progressively increase. In fact, urine parameters in patients with hepatorenal syndrome are similar to those in patients with hypovolemia. The pathogenesis of hepatorenal syndrome is not fully understood, but it can be assumed that vasoconstriction of the renal vessels with a subsequent decrease in renal blood flow is the primary moment responsible for the development of hepatorenal syndrome. According to some researchers, hepatorenal syndrome develops as a result of a decrease in plasma volume, as well as active diuretic therapy, gastrointestinal bleeding, and paracentesis. Most patients with hepatorenal syndrome die, so careful monitoring of diuretic therapy and volume status is necessary to prevent this syndrome.

In jaundice with high circulating bilirubin levels, its toxic effect on the renal tubules may be the cause of the development of AKI, which is often complicated by hypertension and infection. Patients with cirrhosis have a significantly limited ability to mobilize blood from the visceral (including hepatic) vascular space to increase the BCC. Thus, in response to even very moderate bleeding, these patients may experience severe hypotension with subsequent development of tubular necrosis.

Other severe clinical manifestations include severe edema, ascites, metabolic disorders, significant weight loss, skin itching caused by high hyperbilirubinemia (up to 1300 mmol/l), hypoproteinemia, hypoalbuminemia, etc. The reasons for the decrease in albumin concentration are quite complex and are associated primarily with a violation of protein-synthetic function, as well as with a general increase in the volume of fluid in the body and some other factors.

In the terminal stage of cirrhosis, the central nervous system is affected, and progressive toxic encephalopathy is observed, leading to cerebral edema, followed by death. In patients with hepatic encephalopathy, its usual manifestations are lethargy and mental disorders. Such patients have an increase in the concentration of nitrogen-containing compounds in the blood, while an increase in the concentration of urea in the blood in some cases determines the severity of hepatic encephalopathy. However, some patients with hepatic encephalopathy do not have an increase in blood urea, while other patients with a high concentration of urea in the blood do not show signs of encephalopathy.

Fulminant liver failure progresses from jaundice to encephalopathy extremely rapidly, sometimes in less than a week. In such patients, cytotoxic edema develops in the brain, especially in the gray matter of the cortex. The etiology of cerebral edema is not completely clear. It is obvious that urea and glutamine play a very important role in the pathophysiology of the process. A possible mechanism is known for the increase in osmolarly active intracellular elements, which are formed faster than the brain's ability to adapt by eliminating foreign ions or molecules. Careful analysis of EEG changes is of some value for prognosis, but it has little therapeutic value until nonconvulsive epileptic status is clinically manifested.

Diagnosis of critical increase in intracranial pressure by clinical symptoms is unreliable. In a comatose patient, the onset of brainstem edema ("herniation") is extremely difficult to detect. However, this important point essentially decides the question of the possibility of liver transplantation in a patient whose condition may have already progressed to irreversible structural neurological disorders.

Most patients with cirrhosis have varying degrees of blood coagulation disorders. The coagulation potential of the blood is reduced because the synthesis of liver coagulation factors (I [fibrinogen], II [prothrombin], V, VII, IX, X) and fibrinolytic factors is impaired. Factors II, IX, and X are vitamin K-dependent. Changes in prothrombin time usually reflect the degree of dysfunction well. Leukopenia and thrombocytopenia are due to suppression of bone marrow function, splenomegaly, and DIC. Almost all patients have severe coagulopathy resulting from thrombocytopenia (up to 15 x 109/ml) and a decrease in the concentration of plasma coagulation factors synthesized by the liver. Clinically, this is manifested by an increase in APTT, prothrombin index, and ISC. Coagulopathy necessitates the most precise execution of puncture and catheterization procedures of the central veins and arteries, since the risk of uncontrolled bleeding and the occurrence of large hematomas in the neck, pleural cavity and mediastinum with the slightest technical error is extremely high.

Preoperative preparation and assessment of the patient's condition before liver transplantation

The condition of candidates for a procedure such as liver transplantation varies from chronic fatigue with moderate jaundice to coma with multiple organ failure. The chances of success of liver transplantation are quite high even in patients in extremely serious condition. If the operation is performed in a timely manner, one can expect the reverse development of hepatic encephalopathy with pronounced neurological disorders. Emergency liver transplantation, even in fulminant liver failure, can lead to success in 55-75% of cases. Without transplantation, the prognosis for most patients with fulminant liver failure is extremely poor.

Many physiological abnormalities associated with end-stage liver disease cannot be corrected without transplantation. Therefore, the primary focus of preoperative evaluation should be on the most important physiological abnormalities and on the treatment of pathology that directly threatens the safe induction of anesthesia. For example, pleural effusions may cause a sharp decrease in blood pH, and despite the presence of coagulation abnormalities, thoracentesis may be necessary.

Some rare diseases that are treated by a procedure such as liver transplantation pose additional challenges for anesthesiologists. For example, during transplantation in Budd-Chiari syndrome, which is usually accompanied by extensive hepatic venous thrombosis, active anticoagulation may be required. In children with the rare Crigler-Najjar syndrome (bilirubin-glucuronide-glucuronosyl-transferase deficiency), drugs that prevent the binding of bilirubin to albumin (such as barbiturates) should be avoided.

The impaired volume status of patients with encephalopathy in oliguric renal failure may require removal of excess volume by arteriovenous hemofiltration or hemodialysis before correction of the coagulopathy can be initiated. Plasmapheresis also has theoretical utility in removing potential encephalotoxins, as well as the proven benefit of transfusing blood components. Although plasmapheresis is used in many transplant centers in an attempt to improve conditions for transplantation, the indications and timing of its use have not been definitively defined.

Treatment of increased intracranial pressure should be initiated when symptoms appear and continued throughout the preoperative period. Simple measures, such as raising the upper body by 30°, may help, but excessive reduction of cerebral perfusion pressure should be avoided in patients with hypotension. In some patients, intracranial pressure has been reported to increase with head elevation, probably due to impaired CSF outflow through the foramen magnum as a result of caudal displacement of the brainstem. Mannitol may be used, but with decreased renal excretory function, the use of this osmotically active drug may lead to fluid overload:

Mannitol intravenously 0.25-1 g/kg, the frequency of administration is determined by clinical appropriateness.

Premedication

The components of premedication before liver transplantation are antihistamines (chloropyramine, diphenhydramine), H2 blockers (ranitidine, cimetidine), betamethasone, benzodiazepines (midazolam, diazepam). When prescribing sedatives, the patient's psychoemotional state, its adequacy and the presence of signs of encephalopathy should be taken into account:

Diazepam IM 10-20 mg, once 25-30 minutes before the patient is taken to the operating room or Midazolam IM 7.5-10 mg, once 25-30 minutes before the patient is taken to the operating room

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Diphenhydramine 50-100 mg, once 25-30 minutes before the patient is taken to the operating room or Chloropyramine IM 20 mg, once 25-30 minutes before the patient is taken to the operating room

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Cimetidine IM 200 mg, once 25-30 minutes before the patient is taken to the operating room

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Betamethasone IM 4 mg, once 25-30 minutes before the patient is taken to the operating room.

Basic methods of anesthesia

Induction of anesthesia:

Midazolam IV 2.5-5 mg, single dose

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Ketamine IV 2 mg/kg, single dose

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Fentanyl IV 3.5-4 mg/kg, single dose

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Pipecuronium bromide IV 4-6 mg, single dose or Midazolam IV 5-10 mg, single dose

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Thiopental sodium IV 3-5 mg/kg, single dose (or other barbiturates)

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Fentanyl IV 3.5-4 mcg/kg, single dose

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Pipecuronium bromide IV 4-6 mg, single dose Propofol IV 2 mg/kg, single dose

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Fentangsh IV 3.5-4 mcg/kg, single dose

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Pipecuronium bromide intravenously 4-6 mg, single dose.

During liver transplantation, the risk of surgical hemorrhage with large and rapid blood loss is very high. Therefore, it is necessary to ensure the possibility of rapid replacement of large volumes of fluid. Usually, at least two large-bore peripheral venous cannulas are placed, one of which is used for the use of a rapid transfusion device, and central veins are also catheterized.

The presence of a double-lumen hemodialysis catheter and a Swan-Ganz catheter in both internal jugular veins allows for rapid and effective infusion and replacement of virtually any blood loss. The radial artery is catheterized for continuous monitoring of systemic blood pressure. Invasive monitoring using arterial and pulmonary catheters is standard because significant changes in intravascular volume are common and the donor liver reperfusion period is associated with predictable hypotension. Sometimes, in addition to the radial catheter, a femoral arterial catheter is also placed because distal arterial flow may be compromised during aortic clamping during hepatic artery anastomosis.

In patients with end-stage liver failure, there are multiple causes for delayed gastric emptying, such as ascites or active upper gastrointestinal bleeding. Therefore, aspiration prevention is mandatory, and induction of OA should be either technically rapid or, in patients with hemodynamic instability or significant hypovolemia, conscious intubation under local anesthesia.

The standard induction protocol is the use of midazolam, ketamine (or sodium thiopental), fentanyl, pipecuronium bromide.

A number of authors recommend etomidate as a drug for induction of anesthesia, however, it should be borne in mind that prolonged infusion and general high doses of this drug can cause suppression of adrenal function and require the administration of GCS. In addition, etomidate can aggravate neurological disorders, it is not recommended for use in doses greater than 0.3 mg/kg.

Maintenance of anesthesia:

(general balanced anesthesia based on isoflurane)

Isoflurane 0.6-2 MAC (in minimal-flow mode) with dinitrogen oxide and oxygen (0.3: 0.2 l/min)

Fentanyl IV bolus 0.1-0.2 mg, frequency of administration is determined by clinical appropriateness

Midazolam IV bolus 0.5-1 mg, frequency of administration is determined by clinical appropriateness or (TVVA)

Propofol IV 1.2-Zmg/kg/h

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Fentanyl intravenously bolus 0.1-0.2 mg, the frequency of administration is determined by clinical appropriateness.

Muscle relaxation:

Atracurium besylate 1-1.5 mg/kg/h or Cisatracurium besylate 0.5-0.75 mg/kg/h.

The severity of the patient's initial condition and the specifics of surgical intervention in liver transplantation - the possibility of rapid changes in volemic status, sharp hemodynamic disturbances that occur when the liver is dislocated, the main vessels are clamped, etc. - necessitate ensuring maximum controllability of anesthesia. First of all, this concerns the depth of anesthesia, on which vascular tone and the effectiveness of cardiac activity largely depend. Therefore, preference is given to modern combined anesthesia based on IA as the most mobile and controllable method.

In modern transplantology, the method of choice is OA, the main component of which is a powerful IA (in most cases, isoflurane). Significant disorders of the blood coagulation system exclude the use of RAA methods as potentially dangerous due to possible hemorrhagic complications.

Anesthesia is maintained by drugs that maintain visceral blood flow (opioids, isoflurane, muscle relaxants) except in cases of fulminant liver failure, when the possibility of intracranial hypertension serves as a contraindication to the use of powerful IA.

There are no contraindications for the use of dinitrogen oxide, but this drug is usually avoided due to its ability to expand the intestine and increase the size of gas bubbles entering the bloodstream. Some studies provide results of the use of TVA in liver transplants. The use of infusion of propofol, remifentanil and cisatracurium besilate, i.e. drugs with extrahepatic metabolism, allows avoiding the pharmacological load on the transplant, which has just undergone surgical stress and ischemia, and ensures safe early extubation of the recipient.

The main drugs for anesthesia are the opioid fentanyl (1.2-1.5 mcg/kg/h) and the IA isoflurane (0.5-1.2 MAC) in combination with artificial ventilation of oxygen-nitrous oxide mixture (1:1) used in minimal-flow mode (0.4-0.5 l/min). From the beginning of the operation until the end of the anhepatic period, muscle relaxation is provided by bolus injections of pipecuronium bromide (0.03-0.04 mg/kg/h), and after restoration of blood flow through the transplant, cisatracurium besylate (0.07-0.08 mg/kg/h) is used.

The increase in the volume of distribution in cirrhosis may result in an increase in the initial induction dose of nondepolarizing muscle relaxants and a prolongation of their action. At the same time, the kinetics of fentanyl are virtually unchanged. Although a well-preserved liver graft can rapidly begin metabolizing drugs, many pharmacokinetic changes (e.g., decreased serum albumin, increased volumes of distribution) counteract the detoxifying function of the graft.

An essential point in the operation is the use of warm drugs for infusion, humidified gas mixture, warming blankets and mattresses, insulating covers for the head and limbs. Otherwise, hypothermia develops quickly, which is caused by transfusion, fluid loss during convection and evaporation from open abdominal organs, decreased energy productivity of the liver, and implantation of a cold donor organ.

Orthotopic liver transplantation involves replacing a diseased native liver with a cadaveric organ or a liver lobe from a living related donor; in most cases, it can be performed in an anatomical position. This occurs in three stages: pre-provision, anhepatic, and non-hepatic (post-provision).

The pre-hepatic stage involves dissection of the hepatic porta structures and mobilization. Cardiovascular instability is common at this stage due to hypovolemia, acute third-space losses (ascites), and bleeding from venous collaterals of the abdominal wall, organs, and mesentery. Citrate-induced hypocalcemia, hyperkalemia with rapid transfusion and hemolysis, and obstruction of venous return with liver traction or a sharp fall in IAP also contribute to hemodynamic instability. During sudden volume shifts, initially asymptomatic pericardial effusions may reduce CO. Potential surgical blood loss, often occurring during transection of varices and paracaval veins, may be aggravated by coagulation failure and hemodilution, as well as fibrinolysis. These disorders should be monitored by traditional and special methods of studying the blood coagulation system (prothrombin time, partial thromboplastin time, bleeding time, fibrinogen, fibrin breakdown products and platelet count) and thromboelastography.

To replace blood loss, crystalloids (electrolyte and dextrose solutions), plasma expanders, FFP, and, if indicated, donor EM are used.

Average volumes of infusion therapy components (total volume - 11-15 ml/kg/h):

• crystalloids - 4-6 ml/kg/h;
• colloids - 1-2 ml/kg/h;
• SZP - 4-7 ml/kg/h;
• donor red blood cell mass - 0.5-1.5 ml/kg/h;
• washed autoerythrocytes - 0.2-0.3 ml/kg/h.

To reduce the infusion of donor blood components, a Cell Saver is routinely used to collect and wash extravascular blood. It is used in cases where there is no active infection or malignancy. Many clinics use rapid infusion systems designed to administer warmed fluids or blood products at rates up to 1.5 L/min. These devices are equipped with line pressure monitors, filters, air detectors, and fluid level sensors to minimize damage to blood cells and prevent air infiltration.

The initial metabolic acidosis is aggravated by the resulting periods of hypotension and can be quite pronounced in the absence of metabolic liver function. Sodium bicarbonate is used to treat it:

Sodium bicarbonate, 4% solution, intravenously 2.5-4 ml/kg, the frequency of administration is determined by clinical expediency. However, in case of deep acidosis, an alternative to sodium bicarbonate may be trometamol - a drug that allows avoiding hyperosmolar hypernatremia.

At this stage, oliguria is common, so once prerenal causes are excluded, active therapy with osmotic diuretics or other drugs with a diuretic effect, such as dopamine, should be started at a “renal dose” (2.5 mg/kg/min):

Furosemide intravenously bolus 5-10 mg, frequency of administration is determined by clinical appropriateness

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Dopamine intravenously 2-4 mcg/kg/min through a perfusor, the duration of administration is determined by clinical appropriateness.

Pre-procedural liver transplantation is characterized by the necessity of using comparatively high doses of anesthetics: in this period, the concentration of isoflurane in the gas-anesthetic mixture was, as a rule, maximum - 1.2-2 vol% (1-1.6 MAC), it is necessary to use comparatively much - 3.5 ± 0.95 mcg/kg/h (up to 80% of the total amount) of fentanyl and pipecuronium bromide in the form of bolus injections. This can be explained by the fact that, on the one hand, the body is saturated with pharmacological drugs, on the other hand, this stage is the most traumatic in surgical terms. The pre-procedural stage is characterized by significant mechanical displacements of the liver, arising due to the need for surgical manipulations (tractions, rotations, dislocation) during liver isolation and preparation for hepatectomy. These factors have a very significant impact on systemic hemodynamics, causing periodic decreases in preload under pressure on the inferior vena cava, sharp fluctuations in systemic blood pressure, and relative hypovolemia.

Anhepatic liver transplantation begins with removal of the native liver shortly after cessation of its blood supply and division of the hepatic artery and portal vein, as well as clamping of the supra- and infrahepatic portions of the inferior vena cava. If there is a high risk of rupture of esophageal varices during clamping of the inferior vena cava, a Blakemore catheter can be temporarily inserted. In most transplant centers, in order to avoid a sharp decrease in venous return and a drop in CO, as well as venous congestion in the lower half of the body, intestine and kidneys, a venovenous bypass is used. It allows blood to be collected from the femoral and portal veins and delivered extracorporeally to the axillary vein. A centrifugal pump makes it possible to provide blood transfer in a volume of 20-50% of the normal systemic blood flow. Heparinized line systems can be used in the circuit, which eliminates the need for systemic heparinization. Venous bypass helps preserve renal function and does not increase overall morbidity and mortality, but it may cause air embolism and lead to thrombosis. In addition, the use of venovenous bypass may prolong the procedure and contribute to heat loss. Inotropic support may also be needed to maintain cardiac output during bypass.

Removal of the native liver and implantation of a neohepatic liver are usually accompanied by active surgical manipulations under the diaphragm, decreased respiratory compliance, atelectasis, and hypoventilation. At this stage, the addition of PEEP and increased inspiratory pressure can help minimize these adverse effects. Due to the absence of metabolic liver function during the anhepatic period, the risk of citrate toxicity from rapid blood transfusion increases sharply, so calcium administration is necessary to keep the ionized calcium content above 1 mmol/L. Calcium chloride is most often used in boluses of 2-4 ml.

During the anhepatic period, progressive hyperkalemia can be treated with insulin infusion despite the absence of the liver, but metabolic acidosis, including lactate, remains largely uncorrected.

During the anhepatic stage, the consumption of anesthetics is usually quite moderate. The required concentration of isoflurane can be reduced to 0.6-1.2 vol% (0.5-1 MAC), the need for fentanyl is reduced to 1 ± 0.44 μg/kg/h. In most patients, the need for muscle relaxants is sharply reduced.

The nonhepatic (post-reperfusion) stage begins with anastomosis of the hepatic and portal veins and initiation of blood flow through the graft. Even before the vessels are unclamped, the graft is flushed with albumin or blood from the portal vein to remove air, cellular debris, and preservative solution. However, the final unclamping may release large amounts of potassium and acid metabolites into the circulation. Arrhythmias, hypotension, and cardiac arrest may occur at this point, and the anaesthetist must be prepared to treat these metabolic complications immediately. Inotropic support is needed to treat hypotension due to myocardial depression by vasoactive mediators, right heart failure due to overload, or venous air embolism. Pulmonary thromboembolism may also be the cause of cardiovascular collapse during reperfusion.

As a rule, after correction of sharp hemodynamic shifts that occur during reperfusion through the transplant, a period of relative hemodynamic stability is observed. However, the second wave of CVS depression occurs when blood flow through the hepatic artery is started. At this stage, there are no signs of right heart overload, there are no prerequisites for hypervolemia, and pronounced vascular dystonia accompanied by a decrease in CO is caused by the second toxic wave, i.e., the washout of acidic metabolites from the arterial system of the liver. Sustained systemic vasodilation develops quite quickly, characterized by a marked decrease in diastolic pressure (up to 20-25 mm Hg). To correct this condition, it is sometimes necessary to connect vasopressors (mesaton, norepinephrine), and infusion therapy is activated.

In addition to the above, the reperfusion period is accompanied by the need to correct the disorders of the hemocoagulation system. The initial state of hypocoagulation caused by liver failure and impaired protein-synthetic function of the liver is aggravated by the need for systemic administration of sodium heparin before the start of hardware venovenous bypass. After its termination, it is necessary to neutralize free sodium heparin with protamine. However, this moment can be potentially dangerous, on the one hand, due to possible thrombosis of vascular anastomoses when eliminating hypocoagulation, and on the other hand, due to increased tissue bleeding and ongoing bleeding if neutralization is not performed. An indicator that can be considered acceptable by the time of completion of vascular anastomoses is APTT equal to 130-140 sec. With these indicators, sodium heparin is not used. At the same time, active infusion of FFP (7-8 ml/kg/h) is performed, protease inhibitors (aprotinin), a-aminocaproic acid are used. Constant monitoring of the coagulation status seems to be very important, since severe coagulopathy may develop during the operation. Some coagulopathies that occur during liver transplantation may be associated with undesirable sequestration of sodium heparin and its subsequent washout from the transplant when it is included in the systemic bloodstream.

The postreperfusion stage is characterized by a gradual increase in glucose (up to 12-20 mmol/l) and lactate (up to 8-19 mmol/l). However, as soon as the graft begins to function, hemodynamic and metabolic stability is gradually restored. The introduction of a large volume of FFP (up to 3-4 l) and red blood cell mass can cause an increase in the plasma citrate concentration, which, together with previous active sodium bicarbonate therapy, can cause metabolic alkalosis. The need for inotropic support usually decreases, and diuresis increases even in patients with previous hepatorenal syndrome, although in most cases its stimulation with furosemide is necessary. The operation ends with some form of restoration of bile outflow - a direct anastomosis of the recipient's bile ducts and the graft or a Roux choledochojejunostomy.

[ 7 ], [ 8 ], [ 9 ], [ 10 ], [ 11 ]

Liver transplantation in children

Approximately 20% of orthotopic transplants worldwide are performed in children, and a significant proportion of these recipients are under 5 years of age. The most common cause of liver failure in children is congenital biliary atresia, followed by inborn errors of metabolism, which include alpha-1 antitrypsin deficiency, glycogen storage diseases, Wilson disease, and tyrosinemia. The last three conditions primarily involve biochemical defects of the hepatocytes and can therefore only be cured by a procedure such as liver transplantation.

Some aspects of orthotopic liver transplantation in children are unique. For example, sick children with biliary atresia are often decompressed by the Kasai procedure (choledochoejejunostomy) already in the first days or weeks of life. Previous intestinal surgery can complicate laparotomy during the pre-procedural stage of liver transplantation, as well as restoration of bile drainage. Many authors note that venovenous bypass is often not feasible in patients up to 20 kg, since venous overload of the lower half of the body, accompanying compression of the portal and inferior vena cava, can lead to oliguria and intestinal complications in young children of this group. A graft that is too large can sequester a significant portion of the blood volume, increasing the risk of excessive potassium release after reperfusion and leading to severe hypothermia.

However, our own experience has shown the possibility of successful transplantation using veno-venous bypass in children weighing 10-12 kg. We can note that a problem specific to small children is temperature imbalance. Moreover, the body temperature can shift both towards hypothermia, which is aggravated by extracorporeal bypass, and towards an increase in temperature to 39° C. In our opinion, the most effective method of combating hypo- and hyperthermia is the use of water thermal mattresses and thermal suits, which make it possible to remove excess heat production or warm the patient, depending on the circumstances.

According to world statistics, the overall one-year survival of children after orthotopic liver transplantation is 70-75%, but the results for younger (less than 3 years) and small (less than 12 kg) sick children are not so rosy (one-year survival is 45-50%). The main reason for the lower survival is considered to be the high incidence of hepatic artery thrombosis in young children, which, in turn, is associated with the size of the artery and the use of a reduced-size split liver.

Correction of violations

In a well-functioning graft, metabolic acids, including lactate, continue to be metabolized, and systemic alkalosis that occurs late in the operation may require correction. Careful postoperative pulmonary care is necessary because complications such as diaphragmatic injury, nosocomial pneumonia, and RDS with massive blood transfusion may occur. Primary failure of graft function is now a relatively rare complication of liver transplantation, possibly due to the widespread use of modern preservatives and improvements in surgical and anesthetic techniques.

The precise phasing of the operation determines the tactics of the anesthesiologist's actions in accordance with the surgical situation and the patient's condition. The use of modern drugs - isoflurane, midazolam, myorelaxants with extrahepatic metabolism (cisatracurium besilate) allows to increase the controllability of anesthesia and ensure early extubation of patients.

[ 12 ], [ 13 ], [ 14 ], [ 15 ]

Liver transplant: patient assessment after surgery

The use of modern anesthesia techniques based on modern anesthetics isoflurane, sevoflurane has made it possible to sharply reduce the time of postoperative artificial and assisted ventilation of the lungs to 2-4 hours. Early extubation significantly reduces the number of possible complications from the respiratory system, but at the same time leaves the problem of adequate and reliable pain relief in the postoperative period very urgent. For this purpose, opioids are traditionally used - morphine, trimeperidine, tramadol, as well as ketorolac and other drugs. Doses are selected strictly individually. The appointment of immunosuppressants (prednisolone, cyclosporine) causes the presence of almost constant hypertension in these patients. Some patients experience headaches and convulsive readiness during the early adaptation period.