Kharitonova T. V. (St. Petersburg, Mariinsky Hospital)
Mamontov S.E. (St. Petersburg, Medical Unit No. 18)

Infusion therapy is a serious tool for an anesthesiologist-resuscitator, and can provide an optimal therapeutic effect only if two essential conditions are met. The doctor must clearly know the purpose of using the drug and have an idea of ​​its mechanism of action.

Rational fluid therapy is the most important aspect of maintaining hemodynamic function during surgery. Although it is certainly necessary to maintain acid-base and electrolyte balance, oxygen transport, and normal blood coagulation during surgery, normal intravascular volume is the main parameter of life support.

Intraoperative fluid therapy should be based on an assessment of physiological fluid requirements, comorbidities, anesthetic medications, anesthesia technique, and fluid losses during surgery.

The main goal of fluid therapy in critical situations is to maintain adequate cardiac output to ensure tissue perfusion at the lowest hydrostatic pressure in the capillary lumen. This is necessary in order to prevent fluid leakage into the interstitium.

Figure 1. Frank-Starling curves under different conditions (bottom - hypokinesia, middle - normal, top - hyperkinesia).

Hemodynamics

Maintaining optimal intravascular volume (IV) and ventricular preload is the basis for normal cardiac function. The principles expressed by E.G. Starling and O. Frank at the beginning of the twentieth century still shape our understanding of circulatory physiology, pathophysiological mechanisms and methods for their correction (Fig. 1).

The state of myocardial contractility under various conditions, such as hypokinesia - circulatory failure during hemorrhagic shock, or hyperkinesia - the early phase of septic shock, are examples of situations in which Starling forces operate relatively flawlessly.

However, there are many situations that cast doubt on the universality of the Frank-Starling law for all critical conditions.

Maintaining preload (it is characterized by ventricular end-diastolic volume - EDV) is the basis for correcting unstable hemodynamics. Preload is influenced by a huge number of factors. Understanding that EDV is a determining factor of preload is a key point in studying the pathophysiology of hypovolemia and acute circulatory failure, since pressure in the ventricular cavity in critical conditions is not always a reliable indicator of preload.

Figure 2. Comparison of changes in central venous pressure and pulmonary arterial pressure depending on the dynamics of preload.

The ratio of EDV to end-diastolic pressure for both ventricles, depending on the degree of their stretching, that is, preload, always leans in favor of volume.

Currently, monitoring is often limited to central venous pressure (CVP), although right ventricular end-diastolic pressure or pulmonary capillary wedge pressure (PCWP) is sometimes used to assess preload. Comparison of CVP, end-diastolic pressure and preload can help to understand how disparate these monitoring parameters are (Fig. 2).

It is very important to understand why such monitoring is imperfect. But it is equally important to know how to correctly interpret its results in order to ensure the maintenance of adequate hemodynamic function.

The level of central venous pressure is traditionally used to judge the magnitude of venous return and the volume of intravascular fluid. However, with the development of many critical conditions, desynchronization of the work of the left and right hearts is observed (biventricular phenomenon). This phenomenon cannot be detected with a banal study of central venous pressure. However, echocardiography or other invasive methods make it possible to accurately assess myocardial contractility and determine further tactics of infusion and drug support. If, nevertheless, a biventricular phenomenon has already been identified, then it should be regarded as a sign that does not give much hope for success. A delicate balancing act between fluid therapy, inotropes, and vasodilators will be required to achieve a positive outcome.

When right ventricular failure develops following myocardial failure of the left ventricle (for example, with mitral defects), the CVP will reflect the operating conditions of the left half of the heart. In most other situations (septic shock, aspiration syndrome, cardiogenic shock, etc.), focusing on CVP numbers, we are always late both in diagnosis and in intensive care.

Arterial hypotension as a result of decreased venous return is a convenient scheme for explaining the clinical physiology of shock, but in many ways these ideas are mechanistic.

The English physiologist Ernest Henry Starling formulated his ideas on these issues in a famous report of 1918. In this report, he refers to the work of Otto Frank (1895) and some data from his own studies on a cardiopulmonary drug. The law first formulated and proclaimed stated that “the length of the muscle fiber determines the work of the muscle.”

O. Frank's studies were carried out on isolated frog muscle using a kymograph that had just appeared in physiological laboratories. The Frank-Starling addiction received the name “law of the heart” with the light hand of Y. Henderson, a very talented and inventive experimenter, who at that time focused all his attention on the intravital study of cardiac activity in humans.

It should be noted that the Frank-Starling law ignores the difference between the length of the fibers and the volume of the heart muscle. It has been argued that the law should measure the relationship between ventricular filling pressure and ventricular performance.

It seems that everyone was just waiting for the appearance of such a “convenient” law, since over the next decades of the beginning of the last century there was literally a flurry of various clinical and physiological explanations of all changes in circulatory pathology from the standpoint of the “law of the heart.”

Thus, the Frank-Starling law reflects the state of the heart pump and capacitance vessels as a single whole system, but does not reflect the state of the myocardium.

Conventional indicators of adequate intravascular volume and perfusion, such as central venous pressure, can be used successfully in monitoring patients without significant vascular pathology and volemic disorders who undergo elective surgical interventions. However, in more complex cases, for example, in patients with concomitant cardiac pathology, severe types of shock, careful monitoring is required - pulmonary artery catheterization, as well as transesophageal echocardiography. In critical situations, only these monitoring methods can help adequately assess preload, afterload and myocardial contractility.

Oxygen transport

The delivery of oxygen to tissues is determined by the magnitude of cardiac output and the volumetric oxygen content of arterial blood.

The oxygen content in arterial blood depends on the amount of hemoglobin, its oxygen saturation and, to a small extent, on the amount of oxygen dissolved in the plasma. Thus, an adequate number of red blood cells is an indispensable condition for maintaining normal oxygen levels in arterial blood, and, accordingly, its delivery. At the same time, in almost all cases of blood loss, oxygen starvation of tissues occurs not due to hemic hypoxia, but due to circulatory hypoxia. Thus, the doctor is faced with the task, first of all, to increase the volume of circulating blood and normalize microcirculation, and then restore blood functions (transport, immune, etc.). Possible alternatives to red blood cells are modified hemoglobin preparations and perfluorane.

Although donor screening has significantly reduced the risk of transfusion transmission of hepatitis and human immunodeficiency virus, numerous transfusion complications and shelf life limitations remain. Alternatives to blood transfusion include increasing cardiac output, increasing tissue oxygen utilization, and maintaining a high oxygen saturation of arterial hemoglobin. However, we must not forget that after surgery, oxygen consumption increases sharply - the so-called postoperative hypermetabolic state.

Electrolyte balance and acid-base status

Despite the great importance in patient management of assessing and correcting the concentrations of calcium, magnesium and phosphates, the main electrolytes during the intraoperative period are sodium, potassium and chlorides. Their concentration is most affected by the infusion of crystalloid solutions.

Saline solutions (saline sodium chloride solution and Ringer's lactate) affect the concentration of sodium chloride outside the cell and the acid-base state. During surgery and in the postoperative period, the concentration of aldosterone in the blood increases sharply, which leads to an increase in sodium reabsorption in the kidney tubules. This requires equilibrium reabsorption of a negative anion (ie, chloride) or secretion of a hydrogen or potassium ion to maintain electrical neutrality of the renal tubules. When using a physiological solution of sodium chloride, the secretion of potassium and hydrogen ions sharply decreases, as a result of which hyperchloremic metabolic acidosis can develop.

The short residence time in the lumen of the vessel and the relatively low sodium content are arguments against the use of saline sodium chloride solution for the treatment of surgical blood loss. The most commonly used solutions in practice are saline sodium chloride and balanced salt solutions, such as lactated Ringer's solution. The best saline solutions contain potassium, but they should be used with caution in patients with hyperkalemia, especially those with renal failure. You should also keep in mind that Ringer's lactate solution contains calcium. Therefore, Ringer's lactate solution should not be used in cases where citrated blood infusion is planned.

The use of Ringer-lactate solution is more physiological, since the sodium/chlorine ratio is maintained and acidosis does not develop. Infusion of a large amount of Ringer-lactate solution in the postoperative period can lead to alkalosis, since a lot of bicarbonate is formed as a result of the metabolism of lactate. In this situation, it may be advisable to add potassium and calcium to these standard solutions.

Glucose

The inclusion of glucose in the intraoperative infusion therapy program has been discussed for quite some time. Traditionally, glucose has been administered intraoperatively to prevent hypoglycemia and to limit protein catabolism. Prevention of hypo- and hyperglycemia is especially important in patients with diabetes mellitus and liver disease. In the absence of diseases that greatly affect the metabolism of carbohydrates, you can do without glucose solutions.

Hyperglycemia, accompanied by hyperosmolarity, osmotic diuresis and acidosis of brain tissue are the consequences of excessive ingestion of glucose solutions. Since the brain functions only on glucose, under hypoxic conditions anaerobic metabolism of glucose begins and acidosis develops. The longer the duration of acidosis, the more likely it is that nerve cells will die or be permanently damaged. In these situations, glucose solutions are absolutely contraindicated. The only indication for intraoperative use of glucose solutions is the prevention and treatment of hypoglycemia.

Clotting factors

Deficiency of coagulation factors can lead to bleeding and is therefore an indication for the use of blood products, including fresh frozen plasma, platelets or cryoprecipitate. The causes of deficiency of coagulation factors can be: hemodilution, disseminated intravascular coagulation, inhibition of hematopoiesis, hypersplenism and deficiency of synthesis of coagulation factors. In addition, platelet dysfunction may occur, both endogenous (for example, with uremia) and exogenous (taking salicylates and non-steroidal anti-inflammatory drugs). Regardless of the cause, identification and confirmation of coagulation disorders is strictly necessary before transfusion of blood components.

The most common coagulopathy during surgery is dilution thrombocytopenia, which often occurs with massive transfusions of red blood cells, colloid and crystalloid solutions.

Deficiency of coagulation factors in the absence of liver dysfunction is rare, but it must be remembered that only 20-30% of labile coagulation factors (factor VII and VIII) are retained in preserved blood. The indication for platelet transfusion in a surgical patient is severe thrombocytopenia (from 50,000 to 75,000). An extension of the standard clotting time by 2-4 times is an indication for infusion of fresh frozen plasma, and a fibrinogen level of less than 1 g/l in the presence of bleeding indicates the need to use cryoprecipitate.

Infusion therapy

Quantitative aspects

The volume of fluid therapy during surgery is influenced by many different factors (Table 1). In no case should you ignore the results of assessing the state of intravascular volume (IVC) of fluid before surgery.

Hypovolemia is often combined with chronic arterial hypertension, causing an increase in total vascular resistance. The volume of the vascular bed is also affected by various medications that the patient took for a long time before surgery or that were used as preoperative preparation.

If the patient has disorders such as nausea, vomiting, hyperosmolarity, polyuria, bleeding, burns or malnutrition, then preoperative hypovolemia should be expected. Often it remains unrecognized due to the redistribution of VSO fluid, chronic blood loss, as well as unchanged and sometimes even growing body weight. The causes of volemic disorders in such a situation may be: intestinal dysfunction, sepsis, acute pulmonary injury syndrome, ascites, pleural effusion and the release of hormonal mediators. All these processes are often accompanied by an increase in capillary permeability, resulting in a loss of intravascular fluid volume into the interstitial and other spaces.

Correction of preoperative fluid deficiency is the cornerstone in the prevention of severe arterial hypotension and hypoperfusion syndrome during induction of anesthesia.

When compensating for a deficiency, it should be remembered that in the absence of hypovolemic shock, the maximum permissible rate of fluid administration is 20 ml/kg/hour (or in terms of body surface area 600 ml/m2/hour). Hemodynamic stabilization, necessary for the initiation of anesthesia and surgery, is characterized by the following indicators:

Blood pressure not lower than 100 mm Hg. Art.

CVP within 8 - 12 cm of water. Art.

diuresis 0.7 - 1 ml/kg/hour

Despite all precautions, induction is in any case accompanied by a decrease in venous return. Intravenous anesthetics used for induction of anesthesia, including sodium thiopental and propofol, significantly reduce total vascular resistance and can also reduce myocardial contractility. Other drugs are also used to maintain anesthesia - for example, etomidate, brietal, dormicum or opiates in high doses can also provoke arterial hypotension due to inhibition of the sympathoadrenal system. Muscle relaxants can release histamine (curare and atracurium) and reduce overall vascular resistance, or increase the volume of venous depots due to pronounced muscle relaxation. All inhalational anesthetics reduce vascular resistance and inhibit myocardial contractile function.

Table. Factors influencing the volume of intraoperative infusion therapy

Artificial pulmonary ventilation (ALV), started immediately after induction of anesthesia, is especially dangerous for a patient with hypovolemia, since positive inspiratory pressure sharply reduces preload. The use of regional methods of pain relief, for example, epidural and spinal anesthesia, can be a real alternative to general anesthesia if there are conditions and time to replenish fluid deficiency. However, all these methods are accompanied by sympathetic blockade, extending two to four segments above the sensory block, and this can be detrimental for a patient with hypovolemia due to the deposition of blood in the lower extremities.

In practice, two preventive measures are used that have proven themselves to be effective in preventing arterial hypotension during epidural and spinal anesthesia: tight bandaging of the lower extremities with elastic bandages and preinfusion of a 6% solution of hydroxyethyl starch (Refortan).

In addition to the effects of anesthesia, the effects of surgery itself cannot be discounted. Bleeding, removal of ascitic or pleural effusion, the use of large amounts of fluid to wash the surgical wound (especially in cases where massive absorption of this fluid is possible, such as during resection of prostate adenoma) - all this affects the volume of intravascular fluid.

The patient's position, the surgical technique itself, and temperature changes have a significant impact on venous return and vascular tone. Many general anesthetics are vasodilators and their use increases heat loss through the skin by approximately 5%. Anesthesia also reduces heat production by about 20-30%. All these factors contribute to increased hypovolemia. You should also take into account the redistribution of fluid and its evaporation from the surgical field (regardless of what kind of operation it is).

Over the past 40 years, a wealth of perspectives on fluid management during abdominal and thoracic surgery have been published. Before the modern theory of intravascular fluid volume redistribution emerged, it was believed that salt and water retention during surgery dictated requirements for limiting fluid infusion to avoid volume overload. This point of view was based on the recording of increased concentrations of aldosterone and antidiuretic hormone during surgery. The fact that the release of aldosterone is a response to operational stress is a long and unconditionally proven fact. Moreover, continuous positive pressure ventilation further promotes oliguria.

More recently, evidence of fluid loss into the “third space” has emerged, and most clinicians have agreed that volume deficits in both extracellular and intravascular fluid occur during surgery.

For many years, especially before the advent of invasive methods for monitoring preload and cardiac output, clinicians were only able to make empirical calculations of fluid resuscitation based on surgical location and duration. In this case, for abdominal interventions, the infusion rate is approximately 10 to 15 ml/kg/hour of crystalloid solutions, plus solutions necessary to replace blood loss and administer drugs.

For thoracic procedures, the infusion rate ranges from 5 to 7.5 ml/kg/hour. Although such strict limits are no longer adhered to, it must be said that such infusion rates provide some confidence in the adequacy of replenishing the extracellular fluid deficiency. With the introduction into clinical practice of modern hemodynamic monitoring and new methods of surgical interventions, doctors no longer use schemes, but provide an individual approach to each patient based on knowledge of the pathophysiology of a particular disease, the method of surgical intervention and the pharmacological properties of the anesthetics used.

During surgery, the volume of fluid required to replenish blood loss and administer medications is added to the volume of infusion therapy. Blood loss is always accompanied by fluid redistribution and loss of extracellular and intracellular fluid volume. It should be remembered that the main threat to the patient is not the loss of red blood cells, but hemodynamic disorders, therefore the main task of infusion therapy is to compensate for the volume of blood volume. Blood loss is replaced so that the volume of injected fluid is greater than the volume of lost blood. Canned blood is not an optimal transfusion medium for this purpose: it is acidotic, has a low oxygen capacity, and up to 30% of its red blood cells are in the form of aggregates that block the capillaries of the lungs. When replacing blood loss with crystalloid solutions, three times more crystalloid solutions are required to maintain an adequate volume of intravascular fluid than was lost in blood.

It is also necessary to take into account fluid losses during abdominal operations, but such losses can be very difficult to estimate. It was previously believed that after major abdominal surgery, fluid restriction was required to prevent the development of pulmonary edema and congestive heart failure. This can indeed happen, since in the postoperative period there may be a shift of fluid towards the interstitial space. It should be assumed that this redistribution is based on a change in vascular permeability. The reason for this change in permeability may be the release of proinflammatory cytokines, including interleukins 6 and 8, as well as tumor necrosis factor (TNFa) as a result of the stress response to surgery. Although there are few reproducible studies on this subject, a possible source of endotoxemia is ischemic or traumatized mucosa.

Despite all of these mechanisms, over the course of 25 years, a strong point of view has emerged that adequate fluid therapy is necessary during surgery to maintain preload and cardiac output. In cases of deterioration of myocardial contractility, infusion therapy is carried out in such a volume as to maintain a minimum end-diastolic pressure (that is, PCWP should be in the range from 12 to 15 mm Hg), which allows the use of drugs for inotropic support against this background. The need to limit fluid in the postoperative period and control diuresis is dictated by the pathophysiology of the underlying disease.

Table 3. Criteria for choosing solutions for infusion therapy in the intraoperative period

• Endothelial permeability
• Oxygen transport
• Clotting factors
• Colloid-oncotic pressure
• Tissue swelling Electrolyte balance
• Acid-base state
• Glucose metabolism
• Brain disorders

Qualitative aspects

The main arguments in favor of choosing a particular solution should be based on the correct interpretation of various indicators characterizing a given clinical situation, and the comparability of the physicochemical properties of the drug with it (see Appendix).

Colloidal solutions have high oncotic pressure, as a result of which they are distributed predominantly in the intravascular sector and move the water of their interstitial space there. The larger the solute molecule, the stronger the oncotic effect and the lower its ability to leave the vascular bed by exiting into the interstitium or filtering in the glomeruli of the kidneys. At the same time, the valuable quality of medium molecular colloids is their ability to improve the rheological properties of blood, which leads to a decrease in afterload and an increase in the volume of tissue blood flow. The disaggregant properties of dextrans make it possible to use these drugs to “unblock” the capillary bed (however, at a dose of more than 20 ml/kg/day, there is a real danger of developing coagulopathy).

Crystalloid solutions are distributed in approximate proportions: 25% in the intravascular space, 75% in the interstitial space.

Glucose solutions stand separately: volume distribution is 12% in the intravascular sector, 33% in the interstitium, 55% in the intracellular sector.

Below we present (Table 3) the effect of various solutions on the central nervous system, the volume of interstitial fluid and the volume of extracellular fluid per 250 ml of injected solution.

Table 3. Changes in the volume of liquid sectors with the introduction of 250 ml solutions

Compensating for insufficient oxygen transport and the coagulation system requires transfusion of blood components. The choice remains with crystalloid solutions if the main disturbances concern electrolyte balance or acid-base status. The use of glucose solutions, especially in cases of cerebrovascular accidents and surgical interventions, is currently not recommended, since they aggravate acidosis in brain tissue.

The greatest number of disputes over the past 30 years has arisen among supporters of colloids and crystalloids as means of compensating surgical blood loss. Ernest Henry Starling (1866-1927) - founder of the doctrine of the influence of colloidal forces on the transport of liquids through membranes. The principles that formed the basis of the famous Starling equation back in 1896 remain relevant today. The balance of forces included in the well-known Starling equation is the most convenient model for not only explaining most of the troubles observed in conditions of impaired vascular endothelial permeability, but also predicting the effects that arise when prescribing various infusion drugs (Fig. 3).

Figure 3. Balance of Starling forces at the level of pulmonary capillaries

It is known that approximately 90% of the total plasma colloid-oncotic pressure (COPP) is created by albumin. Moreover, this is the main force that is capable of holding liquid inside the capillary. Controversy began ever since studies appeared that proclaimed that when EDP decreases, water begins to accumulate in the lungs. Opponents of these authors wrote that increasing capillary permeability allows colloidal particles to freely pass through membranes, which neutralizes shifts in colloid-oncotic pressure. It has also been shown that colloids can also cause a lot of trouble - their large particles “clog” the lymphatic capillaries, thereby attracting water into the pulmonary interstitium (this argument regarding colloids of low and medium molecular weight remains completely valid today).

Of interest are data from a meta-analysis of eight randomized clinical trials comparing infusion therapy with colloids or crystalloids. The difference in mortality in trauma patients was 2.3% (more in the group where colloid solutions were used), and 7.8% (more in the group where crystalloids were used) in patients without trauma. It was concluded that in patients with obviously increased capillary permeability, the administration of colloids can be dangerous, but in all other cases it is effective. A large number of experimental models and clinical studies have not established a clear relationship between colloid-oncotic pressure, the type of solution administered and the amount of extravascular water in the lungs.

Table 4. Advantages and disadvantages of colloids and crystalloids

Thus, in the intraoperative period, the infusion therapy program should be based on a rational combination of two types of solutions. Another question is which solutions to use in critical conditions accompanied by multisystem dysfunction syndrome, and therefore occurring against the background of generalized endothelial damage.

Commercial colloid preparations currently available are dextrans, gelatin solutions, plasma, albumin, and hydroxyethyl starch solutions.

Dextran is a low molecular weight colloidal solution used to improve peripheral blood flow and replenish the volume of circulating plasma.

Dextran solutions are colloids that consist of glucose polymers with an average molecular weight of 40,000 and 70,000 D. The first colloid used in the clinic to replace bcc was a mixed polysaccharide obtained from acacia. This happened during the First World War. After him, gelatin solutions, dextrans and synthetic polypeptides were introduced into clinical practice. However, all of them gave a fairly high frequency of anaphylactoid reactions, as well as a negative effect on the hemocoagulation system. The disadvantages of dextrans that make their use dangerous in patients with multisystem failure and generalized endothelial damage include, first of all, their ability to provoke and enhance fibrinolysis and change the activity of factor VIII. In addition, dextran solutions can provoke dextran syndrome (damage to the lungs, kidneys and hypocoagulation) (Fig. 4.).

Gelatin solutions in critically ill patients should also be used with extreme caution. Gelatin causes an increase in the release of interleukin-1b, which stimulates inflammatory changes in the endothelium. In conditions of a general inflammatory reaction and generalized damage to the endothelium, this danger increases sharply. Infusion of gelatin preparations leads to a decrease in fibronectin concentrations, which may further increase endothelial permeability. The administration of these drugs increases the release of histamine, with well-known unfortunate consequences. There are opinions that gelatin preparations can increase bleeding time, impair clot formation and platelet aggregation, which is due to the increased content of calcium ions in solutions.

A special situation regarding the safety of using gelatin solutions has arisen due to the threat of the spread of the causative agent of transmissible bovine spongiform encephalopathy (“mad cow”), which is not inactivated by conventional sterilization regimes. In this regard, there is information about the danger of infection through gelatin preparations [I].

Uncomplicated hemorrhagic shock can be treated with both colloids and crystalloids. In the absence of endothelial damage, there is virtually no significant difference in lung function after either colloid or crystalloid administration. Similar contradictions exist regarding the ability of isotonic solutions of crystalloids and colloids to increase intracranial pressure.

The brain, unlike peripheral tissues, is separated from the lumen of blood vessels by a blood-brain barrier, which consists of endothelial cells that effectively prevent the passage of not only plasma proteins, but also low-molecular ions, such as sodium, potassium and chlorides. Sodium that does not pass freely through the blood-brain barrier creates an osmotic gradient along the barrier. Decreasing plasma sodium concentration will sharply reduce plasma osmolality and thereby increase the water content of brain tissue. Conversely, an acute increase in sodium concentration in the blood will increase plasma osmolality and cause water to move from brain tissue into the lumen of blood vessels. Because the blood-brain barrier is virtually impermeable to proteins, colloid solutions are traditionally thought to increase intracranial pressure less than crystalloids.

Allergic reactions when using medium- and large-molecular dextrans develop quite often. They arise due to the fact that the body of almost all people has antibodies to bacterial polysaccharides. These antibodies interact with the administered dextrans and activate the complement system, which, in turn, leads to the release of vasoactive mediators.

Plasma

Fresh frozen plasma (FFP) is a mixture of three main proteins: albumin, globulin and fibrinogen. The concentration of albumin in plasma is 2 times the concentration of globulin and 15 times the concentration of fibrinogen. Oncotic pressure is determined to a greater extent by the number of colloid molecules than by their size. This is confirmed by the fact that more than 75% of COD is formed by albumin. The remainder of the plasma oncotic pressure is determined by the globulin fraction. Fibrinogen plays a minor role in this process.

Although all plasma undergoes rigorous screening procedures, there is some risk of transmission of infection: for example, hepatitis C is 1 case in 3,300 doses transfused, hepatitis B is 1 case in 200,000, and HIV infection is 1 case in 225,000 doses.

Transfusion pulmonary edema is an extremely dangerous complication, which, fortunately, occurs infrequently (1 in 5000 transfusions), but nevertheless can seriously overshadow the process of intensive care. And even if complications of plasma transfusion in the form of alveolar pulmonary edema do not occur, then the chance of significantly worsening the condition of the respiratory system and prolonging mechanical ventilation is very high. The cause of this complication is the leukoagglutination reaction of antibodies supplied with the donor's plasma. FFP contains donor leukocytes. In one dose, they can be present in quantities from 0.1 to I x 10." Foreign leukocytes, as well as their own, in patients in critical condition, are a powerful factor in the development of a systemic inflammatory reaction with subsequent generalized damage to the endothelium. The process can be induced by the activation of neutrophils, their adhesion to the vascular endothelium (primarily the vessels of the pulmonary circulation).All subsequent events are associated with the release of biologically active substances that damage cell membranes and change the sensitivity of the vascular endothelium to vasopressors and activate blood coagulation factors (Fig. 5 ).

In this regard, FFP should be used according to the strictest indications. These indications should be limited only to the need to restore coagulation factors.

Hydroxyethylated starch is a synthetic derivative of amylopectin obtained from corn or sorghum starch. It consists of D-glucose units connected in a branched structure. The reaction between ethylene oxide and amylonectin in the presence of an alkaline catalyst adds hydroxyethyl to chains of glucose molecules. These hydroxyethyl groups prevent the hydrolysis of the resulting substance by amylase, thereby lengthening the time it remains in the bloodstream. The degree of substitution (expressed as a number from 0 to 1) reflects the number of glucose chains occupied by hydroxyethyl molecules. The degree of substitution can be controlled by varying the reaction time, and the size of the resulting molecules is controlled by acid hydrolysis of the starting product.

Solutions of hydroxyethylated starch are polydisperse and contain molecules of varying masses. The greater the molecular weight, for example 200,000-450,000, and the degree of substitution (from 0.5 to 0.7), the longer the drug will remain in the lumen of the vessel. Drugs with an average molecular weight of 200,000 D and a degree of substitution of 0.5 were assigned to the pharmacological group "Pentastarch", and drugs with a high molecular weight of 450,000 D and a degree of substitution of 0.7 were assigned to the pharmacological group "Hetastarch".

The weight average molecular weight (Mw) is calculated from the weight fraction of individual molecular species and their molecular weights.

The lower the molecular weight and the more low-molecular fractions there are in a polydisperse preparation, the higher the colloid-oncotic pressure (COP).

Thus, at effective COD values, these solutions have a high molecular weight, which determines the advantages of their use over albumin, plasma and dextrans in conditions of increased endothelial permeability.

Solutions of hydroxyethyl starch are able to “seal” pores in the endothelium that appear in various forms of damage.

Solutions of hydroxyethyl starch usually have an effect on intravascular fluid volume within 24 hours. The main route of elimination is renal excretion. HES polymers with a molecular weight of less than 59 kilodaltons are almost immediately removed from the blood by glomerular filtration. Renal elimination by filtration continues after hydrolysis of larger fragments into smaller ones.

It is assumed that larger molecules do not enter the interstitial space, while smaller ones, on the contrary, are easily filtered and increase the oncotic pressure in the interstitial space. However, the work of R.L. Conheim et al. raise some doubts regarding this statement. The authors suggest that capillaries have both small pores (with a reflection coefficient of 1) and large ones (with a reflection coefficient of 0), and in patients with capillary leak syndrome, it is not the size, but the number of pores that changes.

The oncotic pressure created by HES solutions does not affect the current through large pores, but mainly affects the current through small pores, which are the majority in capillaries.

However, V.A. Zikria et al. and other researchers have shown that the molecular weight distribution and degree of substitution of HES starch solutions significantly influence "capillary leakage" and tissue edema. These authors proposed that hydroxyethyl starch molecules of a certain size and three-dimensional configuration physically “seal” defective capillaries. It's tempting, but how can you test whether such an intriguing model works?

It appears that HES solutions, as opposed to fresh frozen plasma and crystalloid solutions, may reduce capillary leakage and tissue edema. In conditions of ischemia-reperfusion injury, HES solutions reduce the degree of damage to the lungs and internal organs, as well as the release of xanthine oxidase. Moreover, in these studies, animals given hydroxyethyl starch solutions had significantly higher gastric mucosal pH than those given Ringer's lactate solution.

Liver function and mucosal pH in patients with sepsis are significantly improved after the use of hydroxyethyl starch, whereas these functions do not change with albumin infusion.

In hypovolemic shock, infusion therapy using HES solutions reduces the incidence of pulmonary edema compared with the use of albumin and physiological sodium chloride solution.

Infusion therapy containing HES solutions leads to a decrease in circulating levels of adhesion molecules in patients with severe trauma or sepsis. Decreased levels of circulating adhesion molecules may indicate decreased endothelial damage or activation.

In an in vitro experiment, R.E.Collis et al. showed that HES solutions, unlike albumin, inhibit the release of von Willebrand factor from endothelial cells. This suggests that HES is able to inhibit P-selectin expression and endothelial cell activation. Because leukocyte-endothelial interactions determine transendothelial output and tissue infiltration by leukocytes, influencing this pathogenetic mechanism may reduce the severity of tissue damage in many critical conditions.

From all these experimental and clinical observations, it follows that hydroxyethyl starch molecules bind to surface receptors and influence the rate of synthesis of adhesion molecules. Apparently, a decrease in the rate of synthesis of adhesion molecules may also occur due to the inactivation of free radicals by hydroxyethyl starch and, possibly, a decrease in the release of cytokines. None of these effects are detected when studying the effects of solutions of dextran and albumin.

What else can be said about solutions of hydroxyethyl starch? They have another therapeutic effect: they reduce the concentration of circulating factor VIII and von Willebrand factor. This appears to be more the case with Refortan, and may play an important role in patients with initially low concentrations of coagulation factors, or in patients undergoing surgical procedures where reliable hemostasis is absolutely necessary.

The effect of HES on blood coagulation processes in the microvasculature may be beneficial in patients with sepsis. It is impossible not to mention the use of hydroxyethyl starch in kidney donors (with an established diagnosis of brain death), and the subsequent effect of the drug on kidney function in recipients. Some authors who studied this problem noted a deterioration in kidney function after using the drug. HES can cause osmotic nephrosis-like damage in the proximal and distal tubules of the donor kidney. The same damage to the tubules is observed when using other colloids, the infusion of which is carried out in various critical conditions. The significance of such damage for those donors from whom one kidney is taken (that is, healthy people with normal brain function) remains unclear. However, it seems to us that the state of hemodynamics plays a much greater role in the occurrence of such damage, and not the prescription of colloidal solutions.

The dose of hydroxyethyl starch solutions should not exceed 20 ml/kg due to possible dysfunction of platelets and the reticuloendotic system.

Conclusion

Intraoperative infusion therapy is a serious tool for reducing mortality and complications. Maintaining adequate hemodynamics in the intraoperative period, especially preload and cardiac output, is absolutely necessary for the prevention of severe cardiovascular complications both during induction and during main anesthesia. Knowledge of the pharmacology of anesthetics, the correct position of the patient on the operating table, temperature control, respiratory support, choice of surgical technique, area and duration of surgery, degree of blood loss and tissue trauma - these are the factors that should be taken into account when determining the volume of infusion.

Maintaining adequate intravascular fluid volume and preload is important to maintain normal tissue perfusion. Although the quantity of fluid administered is certainly the main consideration, the quality characteristics of the fluid administered must also be considered: the ability to increase oxygen delivery, the effect on blood clotting, electrolyte balance and acid-base status. Authoritative and detailed studies have appeared in the domestic literature, which also prove direct and indirect economic effects when using solutions of hydroxyethyl starch.

In critical conditions, which are accompanied by generalized endothelial damage and a decrease in plasma oncotic pressure, the drugs of choice in the infusion therapy program are solutions of hydroxyethyl starch of various concentrations and molecular weights (Refortan, Stabizol and others).

Literature

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Anesthesiology and resuscitation: lecture notes Marina Aleksandrovna Kolesnikova

Lecture No. 16. Infusion therapy

Lecture No. 16. Infusion therapy

Infusion therapy is a drip or infusion intravenously or subcutaneously of drugs and biological fluids in order to normalize the water-electrolyte, acid-base balance of the body, as well as for forced diuresis (in combination with diuretics).

Indications for infusion therapy: all types of shock, blood loss, hypovolemia, loss of fluid, electrolytes and proteins as a result of uncontrollable vomiting, intense diarrhea, refusal to take fluids, burns, kidney disease; disturbances in the content of basic ions (sodium, potassium, chlorine, etc.), acidosis, alkalosis and poisoning.

The main signs of dehydration of the body: retraction of the eyeballs into the orbits, dull cornea, dry, inelastic skin, palpitations, oliguria, urine becomes concentrated and dark yellow, the general condition is depressed. Contraindications to infusion therapy are acute cardiovascular failure, pulmonary edema and anuria.

Crystalloid solutions are able to replenish the deficiency of water and electrolytes. Use 0.85% sodium chloride solution, Ringer and Ringer-Locke solutions, 5% sodium chloride solution, 5-40% glucose solutions and other solutions. They are administered intravenously and subcutaneously, in a stream (in case of severe dehydration) and drip, in a volume of 10–50 or more ml/kg. These solutions do not cause complications, except for overdose.

The goals of infusion therapy: restoration of bcc, elimination of hypovolemia, ensuring adequate cardiac output, maintaining and restoring normal plasma osmolarity, ensuring adequate microcirculation, preventing aggregation of blood cells, normalizing the oxygen transport function of the blood.

Colloidal solutions are solutions of high molecular weight substances. They help retain fluid in the vascular bed. They use hemodez, polyglucin, reopoliglucin, reogluman. When they are administered, complications are possible, which manifest themselves in the form of an allergic or pyrogenic reaction. Routes of administration: intravenous, less often subcutaneous and drip. The daily dose does not exceed 30–40 ml/kg. They have detoxifying properties. They are used as a source of parenteral nutrition in cases of prolonged refusal to eat or inability to feed by mouth.

Blood and casein hydrolysins are used (Alvesin-Neo, polyamine, lipofundin, etc.). They contain amino acids, lipids and glucose. Sometimes there is an allergic reaction to the injection.

Rate and volume of infusion. All infusions from the point of view of the volumetric rate of infusion can be divided into two categories: those requiring and those not requiring rapid correction of the BCC deficiency. The main problem may be patients who need rapid elimination of hypovolemia. that is, the rate of infusion and its volume must ensure cardiac performance in order to properly supply regional perfusion of organs and tissues without significant centralization of the circulation.

In patients with an initially healthy heart, three clinical landmarks are most informative: mean blood pressure > 60 mm Hg. Art.; central venous pressure – CVP > 2 cm water. Art.; diuresis 50 ml/hour. In doubtful cases, a volume load test is performed: 400–500 ml of crystalloid solution is infused over 15–20 minutes and the dynamics of central venous pressure and diuresis are observed. A significant increase in central venous pressure without an increase in urine output may indicate heart failure, which prompts the need for more complex and informative methods of assessing hemodynamics. Keeping both indicators low indicates hypovolemia, then maintain a high rate of infusion with repeated step-by-step assessment. An increase in diuresis indicates prerenal oliguria (renal hypoperfusion of hypovolemic origin). Infusion therapy in patients with circulatory failure requires clear knowledge of hemodynamics and extensive and special monitoring.

Dextrans are colloidal plasma substitutes, which makes them highly effective in the rapid restoration of bcc. Dextrans have specific protective properties against ischemic diseases and reperfusion, the risk of which is always present during major surgical procedures.

The negative aspects of dextrans include the risk of bleeding due to platelet disaggregation (especially typical for rheopolyglucin), when it becomes necessary to use significant doses of the drug (> 20 ml/kg), and a temporary change in the antigenic properties of the blood. Dextrans are dangerous because they cause a “burn” of the epithelium of the renal tubules and are therefore contraindicated in cases of renal ischemia and renal failure. They often cause anaphylactic reactions, which can be quite severe.

A solution of human albumin is of particular interest, since it is a natural colloid of a plasma substitute. In many critical conditions accompanied by damage to the endothelium (primarily in all types of systemic inflammatory diseases), albumin is able to pass into the intercellular space of the extravascular bed, attracting water and worsening interstitial edema of tissues, primarily the lungs.

Fresh frozen plasma is a product taken from a single donor. FFP is separated from whole blood and immediately frozen within 6 hours after blood collection. Stored at 30°C in plastic bags for 1 year. Given the lability of clotting factors, FFP should be transfused within the first 2 hours after rapid thawing at 37°C. Transfusion of fresh frozen plasma (FFP) carries a high risk of contracting dangerous infections such as HIV, hepatitis B and C, etc. The frequency of anaphylactic and pyrogenic reactions during FFP transfusion is very high, so ABO compatibility must be taken into account. And for young women, Rh compatibility must be taken into account.

Currently, the only absolute indication for the use of FFP is the prevention and treatment of coagulopathic bleeding. FFP performs two important functions at once - hemostatic and maintaining oncotic pressure. FFP is also transfused in case of hypocoagulation, in case of overdose of indirect anticoagulants, during therapeutic plasmapheresis, in acute disseminated intravascular coagulation syndrome and in hereditary diseases associated with deficiency of blood coagulation factors.

Indicators of adequate therapy are clear consciousness of the patient, warm skin, stable hemodynamics, absence of severe tachycardia and shortness of breath, sufficient diuresis - within 30–40 ml/h.

INFUSION THERAPY

Correction of homeostasis

Determination of infusion medium

All infusion media can be divided into:

Classification of infusion media according to V. Hartig, V.D. Malyshev

I. VOLUME REPLACEMENT SOLUTIONS

I. Volume replacement solutions. I.1.Biocolloids.

I. Volume replacement solutions. I. 1.Biocolloids.

Volume-substituting solutions I. Biocolloids.

l. Volume replacement solutions

I. Volume replacement solutions I.3. BLOOD PREPARATIONS

I. Volume-substituting solutions I.4. PREPARATIONS WITH OXYGEN TRANSFER FUNCTION:

II.BASIC INFUSION MEDIUM

II. BASIC INFUSION MEDIUM

III. Corrective infusion media (crystalloids)

III. Corrective infusion media

III. Corrective infusion media

IV. DIURETIC SOLUTIONS

IV. Diuretic solutions

V. PARENTERAL NUTRITION DRUGS

DRUGS FOR PARENTERAL NUTRITION INCLUDED

Modern volume-substituting biocolloids based on hydroxyethyl starch with a molar mass of up to 400,000 Dalton group I

Modern volume-substituting biocolloids based on hydroxyethyl starch with a molar mass of up to 200,000 Daltons, group II

Modern volume-replacing preparations based on hydroxyethyl starch with a molar mass of up to 130,000 Dalton, group III

Modern volume-substituting biocolloids based on hydroxyethyl starch with a molar mass of up to 130,000 Dalton group IV

ROUTES OF ADMINISTRATION OF INFUSION MEDIUM Vascular access

WAYS OF ADMINISTRATION OF INFUSION MEDIUM

PERMISSIBLE VOLUMES OF INFUSION, VOLUME AND RATE OF THEIR ADMINISTRATION

CONTROL OF THE ADEQUACY OF INFUSION THERAPY

Complications related to the route and technique of infusion

I. COMPLICATIONS OF MAIN VEIN PUNCTURE (SUBCLAVIAN CATHETERIZATION):

II COMPLICATIONS OF THE SUBSEQUENT STAY OF THE CATHETER IN VEIN

II COMPLICATIONS OF THE SUBSEQUENT STAY OF THE CATHETER IN VEIN

Literature

Literature

Thank you for your attention!

Efrem Osipovich Mukhin 1766 - 1850

Fedor Ivanovich Inozemtsev 1802 - 1869

Nikolai Ivanovich Pirogov 1810 -1881

Vladimir Aleksandrovich Negovsky 1909 – 2003

2. History of domestic anesthesiology and resuscitation

3. History of domestic anesthesiology and resuscitation

4. History of domestic anesthesiology and resuscitation

1. History of anesthesiology

General anesthesia

Anesthesia components

1. Stages of anesthesia (using the example of ethereal) Gwedel’s classification modified by I.S. Zhorov

2. Stages of anesthesia (using the example of ethereal) Gwedel’s classification modified by I.S. Zhorov

Stages of general anesthesia

1. Study of anamnesis

2. Study of anamnesis

3. Study of anamnesis

4. Study of anamnesis

Objective examination

Special studies

Risk assessment

1.ASA scale

1.ASA physical status scale

Mortality after anesthesia and surgery for each ASA physical status (emergency and elective)

premedication

Drugs used for premedication

Plan of conversation with the patient during the preoperative examination

Goals of pharmacological premedication

Induction of anesthesia

Maintenance of anesthesia

Recovery from anesthesia

1. Complications and difficulties

opens with negative pressure
36

It should be noted that this form of obstruction is not anatomical in origin - but physiological

Final prototypes Nunn used in his research*

Classification of sealing strategies using supraglottic airways:

2. Complications and difficulties

3. Complications and difficulties

1.Monitoring during anesthesia

2.Monitoring during anesthesia

3.Monitoring during anesthesia

Postoperative management