Anaphylaxis and anaphylactic shock - symptoms and treatment

Septic shock is a systemic pathological response to severe infection. It is characterized by fever, tachycardia, tachypnea, and leukocytosis when identifying the source of primary infection. In this case, microbiological blood testing often reveals bacteremia. In some patients with sepsis syndrome, bacteremia is not detected. When arterial hypotension and multiple systemic failure become components of the sepsis syndrome, the development of septic shock is stated.

Causes and pathogenesis of the development of septic shock:

The incidence of sepsis and septic shock has been steadily increasing since the 1930s and is likely to continue to increase. The reasons for this are:

1. Increasing use of invasive devices for intensive care, that is, intravascular catheters, etc.

2. Widespread use of cytotoxic and immunosuppressive drugs (for malignant diseases and transplantations), which cause acquired immunodeficiency.

3. Increase in life expectancy of patients with diabetes mellitus and malignant tumors, who have a high level of predisposition to sepsis.

Bacterial infection is the most common cause of septic shock. In sepsis, the primary foci of infection are often localized in the lungs, abdominal organs, peritoneum, and also in the urinary tract. Bacteremia is detected in 40-60% of patients in a state of septic shock. In 10-30% of patients in a state of septic shock, it is impossible to isolate the culture of bacteria whose action causes septic shock. It can be assumed that septic shock without bacteremia is the result of a pathological immune reaction in response to stimulation by antigens of bacterial origin. Apparently, this reaction persists after pathogenic bacteria are eliminated from the body by the action of antibiotics and other elements of therapy, that is, its endogenization occurs. The endogenization of sepsis may be based on numerous, mutually reinforcing and realized through the release and action of cytokines, interactions of cells and molecules of innate immune systems and, accordingly, immunocompetent cells.

Sepsis, systemic inflammatory response, and septic shock are consequences of an excessive response to stimulation of cells that carry out innate immune responses by bacterial antigens. An excessive reaction of cells of the innate immune system and a secondary reaction of T-lymphocytes and B-cells cause hypercytokinemia. Hypercytokinemia is a pathological increase in the blood levels of agents of autoparacrine regulation of cells that carry out innate immune reactions and acquired immune reactions.

With hypercytokinemia in the blood serum, the content of primary proinflammatory cytokines, tumor necrosis factor-alpha and interleukin-1 increases abnormally. As a result of hypercytokinemia and systemic transformation of neutrophils, endothelial cells, mononuclear phagocytes and mast cells into cellular effectors of inflammation, an inflammatory process devoid of protective significance occurs in many organs and tissues. Inflammation is accompanied by alteration of the structural and functional elements of effector organs.

A critical deficiency of effectors causes multiple systemic failure.

Diagnostics

See also: Shock Index

The definition of refractory or vasodilatory shock varies. In 2021, the American College of Chest Physicians stated that it occurs if there is an inadequate response to high-dose vasopressor therapy, defined as a norepinephrine equivalent dose ≥ 0.5 mg/kg/min.[4]

[15][25][26][27]

Symptoms and signs of septic shock:

The development of a systemic inflammatory response is indicated by the presence of two or more of the following signs:

• Body temperature is higher than 38oC, or below 36oC.

• Respiratory rate greater than 20/minute. Respiratory alkalosis with carbon dioxide tension in arterial blood below 32 mmHg. Art.

• Tachycardia with a heart rate greater than 90/minute.

• Neutrophilia when the content of polymorphonuclear leukocytes in the blood increases to a level above 12x109/l, or neutropenia when the content of neutrophils in the blood is below 4x109/l.

• A shift in the leukocyte formula, in which band neutrophils make up more than 10% of the total number of polymorphonuclear leukocytes.

Sepsis is indicated by two or more signs of a systemic inflammatory reaction when the presence of pathogenic microorganisms in the internal environment is confirmed by bacteriological and other studies.

During pregnancy

Hemorrhagic shock in obstetrics, which occurs during pregnancy, during labor, as well as in the early/late afterbirth period, is one of the significant causes in the structure of maternal mortality, accounting for about 20–25%. The rate of obstetric hemorrhage relative to the total number of births varies between 5-8%.

The specifics of bleeding in obstetrics are:

• The suddenness of their appearance and massiveness.
• High risk of fetal death, which necessitates urgent delivery until stable stabilization of hemodynamic parameters and completion of infusion-transfusion therapy in full.
• Combination with pronounced pain syndrome.
• Rapid depletion of compensatory and protective mechanisms. At the same time, the risk is especially high in pregnant women with late gestosis and in women with complicated labor.

The permissible blood loss during childbirth during its normal course should not exceed 250-300 ml (approximately 0.5% of a woman’s body weight). This amount of blood loss refers to the “physiological norm” and does not negatively affect the condition of the woman in labor. The main causes of acute pathological blood loss during pregnancy with the development of hemorrhagic shock are: ectopic pregnancy , placental abruption/previa, multiple pregnancy, complications during childbirth, cesarean section, uterine rupture.

Features of hemorrhagic shock in obstetric pathology include: its frequent development against the background of a severe form of gestosis in pregnant women, the rapid development of hypovolemia , disseminated intravascular coagulation syndrome, arterial hypotension , and hypochromic anemia .

In case of HS, which developed in the early postpartum period against the background of hypotonic bleeding, a short period of unstable compensation is characteristic, after which irreversible changes quickly develop (persistent hemodynamic disturbances, DIC syndrome with profuse bleeding, respiratory failure and impaired blood coagulation factors with activation of fibrinolysis).

Course of septic shock

In septic shock, hypercytokinemia increases the activity of nitric oxide synthetase in endothelial and other cells. As a result, the resistance of resistive vessels and venules decreases. A decrease in the tone of these microvessels reduces overall peripheral vascular resistance. During septic shock, some of the body's cells suffer from ischemia caused by peripheral circulatory disorders. Peripheral circulation disorders in sepsis and septic shock are consequences of systemic activation of endothelial cells, polymorphonuclear neutrophils and mononuclear phagocytes.

Inflammation of this origin is purely pathological in nature and occurs in all organs and tissues. A critical drop in the number of structural and functional elements of most effector organs is the main link in the pathogenesis of the so-called multiple system failure.

According to traditional and correct ideas, sepsis and a systemic inflammatory response are caused by the pathogenic action of gram-negative microorganisms.

In the occurrence of a systemic pathological reaction to invasion into the internal environment and blood of gram-negative microorganisms, the decisive role is played by:

• Endotoxin (lipid A, lipopolysaccharide, LPS). This heat-stable lipopolysaccharide forms the outer coating of gram-negative bacteria. Endotoxin, acting on neutrophils, causes the release of endogenous pyrogens by polymorphonuclear leukocytes.

• LPS-binding protein (LPBP), traces of which are determined in plasma under physiological conditions. This protein forms a molecular complex with endotoxin that circulates in the blood.

• Cell surface receptor of mononuclear phagocytes and endothelial cells. Its specific element is a molecular complex consisting of LPS and LPSSB (LPS-LPSSB).

Currently, the frequency of sepsis caused by invasion of gram-positive bacteria into the internal environment is increasing. The induction of sepsis by Gram-positive bacteria is usually not associated with their release of endotoxin. Peptidoglycan precursors and other wall components of Gram-positive bacteria are known to trigger the release of tumor necrosis factor-alpha and interleukin-1 by immune cells. Peptidoglycan and other components of the walls of gram-positive bacteria activate the complement system through the alternative pathway. Activation of the complement system at the whole body level causes systemic pathogenic inflammation and contributes to endotoxicosis in sepsis and the systemic inflammatory response.

It was previously thought that septic shock was always caused by endotoxin (a lipopolysaccharide of bacterial origin) released by gram-negative bacteria. It is now generally accepted that less than 50% of cases of septic shock are caused by Gram-positive pathogens.

Disorders of peripheral circulation during septic shock, adhesion of activated polymorphonuclear leukocytes to activated endothelial cells - all this leads to the release of neutrophils into the interstitium and inflammatory alteration of cells and tissues. At the same time, endotoxin, tumor necrosis factor-alpha, and interleukin-1 increase the formation and release of tissue coagulation factor by endothelial cells. As a result, mechanisms of external hemostasis are activated, which causes fibrin deposition and disseminated intravascular coagulation.

Arterial hypotension in septic shock is mainly a consequence of a decrease in total peripheral vascular resistance. Hypercytokinemia and an increase in the concentration of nitric oxide in the blood during septic shock causes dilatation of arterioles. At the same time, through tachycardia, the minute volume of blood circulation increases compensatoryly. Arterial hypotension in septic shock occurs despite a compensatory increase in cardiac output. Total pulmonary vascular resistance increases during septic shock, which can be partly attributed to the adhesion of activated neutrophils to activated endothelial cells of the pulmonary microvessels.

The following main links in the pathogenesis of peripheral circulatory disorders in septic shock are distinguished:

1) increased permeability of the microvascular wall;

2) an increase in microvascular resistance, which is enhanced by cell adhesion in their lumen;

3) low response of microvessels to vasodilating influences;

4) arteriolo-venular shunting;

5) drop in blood fluidity.

Hypovolemia is one of the factors of arterial hypotension in septic shock.

The following causes of hypovolemia (a drop in cardiac preload) in patients in a state of septic shock are identified:

1) dilatation of capacitive vessels;

2) loss of the liquid part of the blood plasma in the interstitium due to a pathological increase in capillary permeability.

It can be assumed that in most patients in a state of septic shock, the drop in oxygen consumption by the body is mainly due to primary disorders of tissue respiration. In septic shock, moderate lactic acidosis develops with normal oxygen tension in the mixed venous blood.

Lactic acidosis in septic shock is considered to be a consequence of decreased pyruvate dehydrogenase activity and secondary accumulation of lactate, rather than a decrease in blood flow in the periphery.

Peripheral circulatory disorders in sepsis are systemic in nature and develop with arterial normotension, which is supported by an increase in minute volume of blood circulation. Systemic microcirculation disorders manifest themselves as a decrease in pH in the gastric mucosa and a decrease in oxygen saturation of blood hemoglobin in the hepatic veins. Hypoergosis of intestinal barrier cells, the action of immunosuppressive links in the pathogenesis of septic shock - all this reduces the protective potential of the intestinal wall, which is another cause of endotoxemia in septic shock.

Meningococcal infection

Meningococcemia is one of the forms of generalized meningococcal infection, characterized by an acute onset with a rise in body temperature to febrile levels, general intoxication, hemorrhagic skin rashes, and the development of infectious-toxic shock.

Clinical manifestations of meningococcal infection:

• Often acute onset or sharp deterioration due to nasopharyngitis.
• High, persistent fever with signs of impaired peripheral circulation. Early signs of fulminant toxic progression of meningococcal infection may be a “two-humped” nature of the temperature curve - the first increase in body temperature to 38.5ºC is reduced with the help of antipyretics, the second (after 9-18 hours) - to 39.5-40ºC without the effect of antipyretics.
• Hemorrhagic rash that appears a few hours or 1-2 days after the onset of fever. The typical localization of the rash is the outer surface of the thighs and legs, buttocks, feet, hands, and lower abdomen. Often a hemorrhagic rash is preceded or combined with a polymorphic roseolous or roseolous papular rash with the same localization, less often on the face.
• General cerebral symptoms: intense headache, “cerebral vomiting”, possible disturbances of consciousness, delirium, hallucinations, psychomotor agitation, convulsions.
• Meningeal syndrome. It usually appears later, against the background of advanced symptoms of meningococcemia.

Threatening syndromes in generalized forms of meningococcal infection are:

• infectious-toxic shock develops during the hyperacute course of meningococcemia. As a rule, symptoms of shock occur simultaneously or after the appearance of a hemorrhagic rash. However, ITS can occur without a rash, so all children with infectious toxicosis should have their blood pressure measured;
• cerebral edema with brainstem dislocation. It manifests itself as impaired consciousness, hyperthermia, severe meningeal symptoms (sometimes their absence in the terminal stage of the disease), convulsive syndrome and unusual changes in hemodynamics in the form of relative bradycardia and a tendency to increase blood pressure. In the terminal stage of cerebral edema there is absolute bradycardia and respiratory arrhythmia.

Urgent Care:

1. Ensure patency of the upper respiratory tract, oxygen therapy.
2. Administer chloramphenicol (chloramphenicol succinate) at a dose of 25-30 mg/kg intramuscularly.
3. Intravenous (if not possible, intramuscular) administration of glucocorticoids in terms of prednisolone 5-10 mg/kg or dexamethasone 0.6-0.7 mg/kg body weight; if there is no effect and it is impossible to transport the patient, it is necessary to re-introduce hormones in the same doses (for ITS stage III, the dose of corticosteroids can be increased 2-5 times).
4. Introduce a 50% solution of metamizole (analgin) 0.1 ml/year of life intramuscularly + 1% solution of diphenhydramine (diphenhydramine) at a dose of 0.1-0.15 ml per year of life intramuscularly (or 2% solution Suprastin solution – 2 mg/kg intramuscularly) + 2% papaverine solution 0.1 ml/year of life).
5. For agitation, convulsive syndrome - 0.5% diazepam solution in a single dose of 0.1 ml/kg body weight (no more than 2 ml per administration) intravenously or intramuscularly, for intractable convulsions again in the same dose .
6. In case of severe meningeal syndrome - intramuscular administration of a 1% furosemide solution at the rate of 1-2 mg/kg intramuscularly or 25% magnesium sulfate solution 1.0 ml/year of life intramuscularly.

Call the resuscitation team for yourself!!! Hospitalization in the intensive care unit of the nearest hospital. If meningococcal infection is suspected, hospitalization is indicated .

Intestinal toxicosis with exicosis is a pathological condition that is a complication of acute intestinal infections (AI) due to exposure to toxic products and significant fluid losses on the body, which leads to disruption of hemodynamics, water-electrolyte metabolism, acid-base reserve, and the development of secondary endogenous intoxication.

In the pathogenesis of toxicosis with exicosis, the leading role is played by dehydration, which leads to a deficiency in the volume of extra- (and in severe cases, intra-) cellular fluid and the volume of circulating blood. The degree of exicosis (dehydration) determines the choice of therapeutic tactics and affects the prognosis.

Severity of dehydration

• II degree of exicosis is divided into IIA and IIB (with loss of body weight 6-7% and 8-9%, respectively).

Measures for dehydration

When starting to rehydrate children with exicosis, it is necessary to determine which route (orally and/or parenterally) and what volume of fluid should be administered to the child, at what speed to administer, and what solutions to use. Oral rehydration is carried out for exicosis of I, IIA degrees, parenteral - for exicosis of IIB and III degrees.

Outpatient treatment is possible (in the absence of other contraindications, see below) for grade I exicosis with oral rehydration.

Oral rehydration therapy

Indications: exicosis I, IIA degrees.

• The necessary solutions are glucose-salt (rehydron, oralit, gastrolit, glucosalan). In children under 3 years of age, it is advisable to combine glucose-saline solutions with salt-free solutions (tea, water, rice water, etc.) in a ratio of 1:1 - for severe watery diarrhea, 2:1 - for loss of fluid mainly through vomiting, 1: 2 – with loss of fluid with perspiration. The administration of saline and salt-free solutions alternates.

The amount of liquid for each hour of administration is divided into ½ teaspoon - 1 tablespoon (depending on age) every 5-10 minutes. If there is vomiting, rehydration does not stop, but is interrupted for 5-10 minutes and then continues again.

Features of the introduction of solutions at the 1st stage (the first 6 hours from the start of treatment):

• for grade I dehydration: 50 ml/kg for 6 hours. + 10 ml/kg b.w. after each loose stool or vomiting;
• for degree IIA dehydration: 80 ml/kg for 6 hours + 10 ml/kg b.w. after each loose stool or vomiting.

At the 2nd stage, maintenance therapy is carried out in the amount of ongoing fluid losses administered at this stage (80-100 ml/kg per day until the loss stops).

Diagnosis of septic shock

• Septic shock - sepsis (systemic inflammatory reaction syndrome plus bacteremia) in combination with a decrease in blood pressure. less than 90 mm Hg. Art. in the absence of visible reasons for arterial hypotension (dehydration, bleeding). Presence of signs of tissue hypoperfusion despite infusion therapy. Perfusion disorders include acidosis, oliguria, and acute disturbances of consciousness. In patients receiving inotropic agents, perfusion abnormalities may persist in the absence of arterial hypotension.
• Refractory septic shock is septic shock lasting more than one hour and refractory to fluid resuscitation.

Control

Addressing the underlying causes of vasodilatory shock, stabilizing hemodynamics, preventing damage to the kidneys, myocardium and other organs due to hypoperfusion and hypoxia, and taking necessary measures to protect against complications including venous thromboembolism are the top priorities during treatment.[24]

Initial treatment aimed at restoring effective blood pressure in patients suffering from refractory shock usually begins with the administration of norepinephrine and dopamine.[24] Vasopressin acts as a second-line agent.[24]

However, high-dose therapy is associated with excessive constriction of the coronary vessels, viscera, and hypercoagulability.[6] Excessive vasoconstriction can cause decreased cardiac output or even fatal cardiac complications, especially in patients with poor myocardial function.[6]

[4][28][29]

In those whose vasodilatory shock is caused by hypocalcemic cardiomyopathy in the context of dilated cardiomyopathy with documented reduction in cardiac ejection fraction and contractility,[17] the use of calcium and active Vitamin D or treatment with recombinant human parathyroid hormone is viable, as many successful cases have been reported. given the physiological role of calcium in muscle contraction.[17][30][31][32]

Successful treatment requires the appropriate and unique contributions of a multidisciplinary team, not only critical care physicians and often, infectious disease specialists, but also respiratory therapy, nursing, pharmacy, and others in collaboration.[24]

List of sources

• Bratus V.D., Sherman D.M. Hemorrhagic shock, pathophysiology and clinical aspects. Kyiv: Nauk. Dumka. 1989.
• Gakaev D. A. Pathophysiological changes in the body during acute blood loss [Text] // Medicine and healthcare: materials of the IV International. scientific conf. (Kazan, May 2021). - Kazan: Buk, 2016. - pp. 37-40.
• Vorobyov A.I., Gorodetsky V.M., Shulutko E.M., Vasiliev S.A. Acute massive blood loss. M.: GEOTAR-MED, 2001.
• Bryusov P.G. Emergency infusion-transfusion therapy for massive blood loss / P.G. Bryusov // Hematology and transfusiology. –1991. – No. 2. – P. 8-13.
• Stukanov M.M. Comparative assessment of infusion therapy options in patients with hemorrhagic shock / M.M. Stukanov et al. //Anesthesiology and resuscitation. – 2011. – No. 2. – P. 27-30.