Prednisolone
Prednisolone is a synthetic glucocorticosteroid drug, a dehydrogenated analogue of hydrocortisone. It has anti-inflammatory, anti-allergic, immunosuppressive, anti-shock effects, increases the sensitivity of beta-adrenergic receptors to endogenous catecholamines.
Interacts with cytoplasmic receptors of glucocorticosteroids (GCS) to form a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells).
Anti-inflammatory effect
associated with inhibition of the release of inflammatory mediators by eosinophils and mast cells; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability, stabilization of cell membranes and organelle membranes (especially lysosomal ones). Acts on all stages of the inflammatory process: inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin inhibits phospholipase A2, suppresses the release of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, which contribute to inflammation, allergies, etc.); synthesis of “pro-inflammatory cytokines” (interleukin-1, tumor necrosis factor alpha, etc.); increases the resistance of cell membranes to the action of various damaging factors.
Immunosuppressive effect
caused by involution of lymphoid tissue, inhibition of the proliferation of lymphocytes (especially T-lymphocytes), suppression of the migration of B-lymphocytes and the interaction of T- and B-lymphocytes, inhibition of the release of cytokines (interleukin-1 and interleukin-2; interferon gamma) from lymphocytes and macrophages and decreased antibody formation.
Antiallergic effect
develops as a result of a decrease in the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a decrease in the number of circulating basophils, suppression of the development of lymphoid and connective tissue, a decrease in the number of T- and B-lymphocytes, mast cells, reducing the sensitivity of effector cells to allergy mediators, suppressing antibody formation, changing the body's immune response.
For obstructive airway diseases
the effect is due mainly to inhibition of inflammatory processes, prevention or reduction of the severity of edema of the bronchial mucous membranes, reduction of eosinophilic infiltration of the submucosal layer of the bronchial epithelium and deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucous membrane. Increases the sensitivity of beta-adrenergic receptors of small and medium-sized bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production.
Suppresses the synthesis and secretion of adrenocorticotropic hormone (ACTH) and, secondarily, the synthesis of endogenous corticosteroids.
Inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.
Emergency conditions in pediatric allergology
In recent years, everyone has recognized the intensive increase in the prevalence of allergic diseases in adults and children. Many allergic diseases have an acute onset with disruption of vital body functions and the development of serious complications. Late and inadequate intensive care significantly increases the risk of death. In this regard, acute conditions of allergic diseases require quick and immediate treatment, based on the doctor’s knowledge of modern algorithms for the management of such patients.
Table 1. Substances that cause anaphylactic shock (medicines, foods, etc.)
Table 2. Cross-reactive substances
Table 3. Causes of acute urticaria and Quincke's edema
Table 4. Determination of the dose of the drug Pulmicort
One of the most severe manifestations in clinical allergology is anaphylactic shock, the prevalence of which is increasing every year, as evidenced by statistical data. The prevalence of anaphylactic shock in different countries ranges from 1/1500 to 1/6000 inhabitants. There are 20 deaths from anaphylactic shock in England each year (1 death per 2.8 million people).
Anaphylactic shock
– an acute systemic allergic reaction of an immediate type, developing in a sensitized organism after repeated contact with an allergen. The most common allergens that cause anaphylactic shock are presented in Table 1.
Anaphylactic shock is often associated with drug and food allergies. Among the medications, anaphylactic shock is most often caused by antibiotics, especially penicillin. Cases of anaphylactic shock have been described with the administration of B vitamins, sulfonamides, iodine-containing agents, dietary supplements, non-steroidal anti-inflammatory drugs, gamma globulin, lidocaine, insulin and others. The cause of anaphylactic shock can be vaccines (for example, DTP - adsorbed pertussis-diphtheria-tetanus vaccine), serums (for the treatment of rabies, botulism, tetanus, against the bites of poisonous snakes and insects). Among food products, nuts, eggs, fish, seafood, and cow's milk are identified as the most common cause of anaphylactic shock.
The international classification provides for the identification of the following forms of anaphylactic shock: T78.0
– anaphylactic shock caused by food products;
T78.2
– anaphylactic shock of unknown etiology;
T80.5
– anaphylactic shock caused by serum preparations;
T88.6
– anaphylactic shock caused by drugs.
According to the mechanism of action, anaphylactic shock is classified into allergic and non-allergic. Allergic anaphylactic shock is divided into IgE-dependent and IgE-independent.
The main clinical manifestations of anaphylactic shock are associated with a decrease in blood pressure and insufficient blood filling of vital organs.
Symptoms of anaphylactic shock usually occur within the first 30 minutes after reintroduction of an intolerant drug or food product. Anaphylactic shock develops at lightning speed, with the appearance of general weakness, anxiety, dizziness, confusion or loss of consciousness. Sometimes there are complaints of tightness in the chest, pain in the heart and abdomen. Nausea, vomiting, decreased hearing and vision, a feeling of heat, chills, urticaria, itchy skin, and the urge to urinate are possible.
Objectively, the patient has pallor of the skin, cold sweat, confusion or loss of consciousness, tachycardia, and decreased blood pressure. Difficulty (stridor) breathing and scattered dry wheezing in the lungs may be noted. The ECG shows symptoms of hypoxia in the form of negative T waves, a decrease in the S-T interval, and conduction disturbances. In peripheral blood there is a shift of the white blood formula to the left and granularity of leukocytes.
In severe cases of anaphylactic shock, secondary complications may develop in the form of dysfunctions of the brain, myocardium, kidneys, intestines, and lungs. In especially severe cases, asphyxia and death may develop.
Clinical observations have shown that intravenous administration of drugs often results in cardiovascular failure, and ingestion of food products results in asphyxia and respiratory failure.
Conventionally, the following forms of anaphylactic shock are distinguished: hemodynamic
(dominance of hypotension, heart pain, arrhythmia, tachycardia),
asphyxia
(bronchospasm, pulmonary edema, hoarseness, stridor breathing due to laryngeal edema),
abdominal
(epigastric pain, involuntary defecation, melena),
cerebral
(psychomotor agitation, stupefaction , convulsions).
An unfavorable outcome of anaphylactic shock is observed in acute malignant disease, in which there is a sharp drop in blood pressure, impaired consciousness and signs of respiratory failure. The degree of reduction in blood pressure is one of the important objective indicators of the severity of anaphylactic shock.
A lethal outcome in anaphylactic shock may be associated with the occurrence of irreversible changes in the functions of the kidneys, gastrointestinal tract, heart, brain, and with the untimeliness and inadequacy of therapy.
The diagnosis of anaphylactic shock is made based on history and clinical signs.
Treatment of anaphylactic shock should be carried out as quickly as possible, since most adverse outcomes of anaphylactic shock develop within 30 minutes after the onset of symptoms.
An anti-shock kit for providing qualified care to patients with anaphylactic shock should include: adrenaline (0.1%) in ampoules (No. 10), norepinephrine (0.2%) in ampoules (No. 5), prednisolone (30 mg) in ampoules (No. 10), dexamethasone (4 mg) in ampoules (No. 10), hydrocortisone hemisuccinate (Solyukortef) 100 mg in ampoules (No. 10), antihistamines (Suprastin, Tavegil) in ampoules (No. 10), aminophylline (2.4%) in ampoules (No. 10) for intravenous administration, strophanthin (0.025%) in ampoules (No. 5), 40% glucose solution in ampoules (No. 20), sodium chloride solution (0.85%) in ampoules (No. 20), solution glucose 5% 100 ml (in bottles) (No. 2), penicillinase 1 million units in ampoules (No. 3), ethyl alcohol 70-100 ml, disposable syringes (1, 2, 5, 10, 20 ml) and needles for them , disposable systems for intravenous infusions (No. 2), rubber tourniquet, mouth dilator, tongue holder, air duct for mouth-to-mouth breathing, oxygen bag, scalpel, suction device.
Stages of anti-shock therapy
If anaphylactic shock occurs due to the drug, its administration must be stopped. The patient is placed on the couch, with the head lower than the feet. The patient's head is turned to the side and the lower jaw is advanced. Apply a tourniquet to the limb above the injection site for a maximum of 25 minutes. Then the injection site is injected with a 0.1% solution of adrenaline (0.3-0.5 ml) with an isotonic sodium chloride solution (4.5 ml) and a bubble with ice or cold water is applied to the injection site for 10-15 minutes. A 0.1% solution of adrenaline is injected into the extremity free from the tourniquet in a dose of 0.1 to 0.5 ml (depending on the age of the child) or at the rate of 0.01 mg/kg body weight. The patient must be taken to the intensive care unit. If there is no effect, the child is again given a 0.1% solution of adrenaline under the skin in the same dose after 5 minutes. The frequency of administration of adrenaline depends on the severity of anaphylactic shock. Repeated administration of small doses of adrenaline is more effective than administration of a large dose once.
If blood pressure does not increase after such therapy, intravenous drip administration of norepinephrine in a 5% glucose solution with the addition of albumin and rheopolyglucin is necessary to maintain the volume of the circulating blood mass. At the same time, glucocorticosteroids (Prednisolone 1-2 mg/kg body weight, or Dexamethasone, or Hydrocotisone), as well as antihistamines (Suprastin or Tavegil), are administered intramuscularly or intravenously. For bronchospasm, bronchospasmodics are prescribed (Ventolin via nebulizer or Eufillin 2.4% intravenous solution in isotonic sodium chloride solution at the rate of 5-7 mg/kg body weight). According to indications, cardiac medications are administered (Strophanthin, Korglykon, Cordiamin). In case of anaphylactic shock, penicillin should be administered intramuscularly with 1 million units of penicillinase, previously dissolved in 2 ml of isotonic sodium chloride solution. If necessary, suction of mucus and vomit from the respiratory tract and oxygen therapy are performed.
The choice of pharmacological drugs depends on the nature of the clinical manifestations of anaphylactic shock. In all cases of anaphylactic shock, adrenaline, glucocorticosteroids and antihistamines should be administered first. Pipolfen, Diprazine, Diphenhydramine should not be administered due to the presence of a pronounced sedative effect. To prevent late complications, glucocorticosteroids are administered intramuscularly every 6 hours.
After discharge from the hospital, the medical documentation should indicate pharmacological agents or food products that can cause manifestations of anaphylactic shock in this patient. Attention should be paid to substances with cross-reactivity (Table 2).
Urticaria and Quincke's edema
Acute urticaria (ICD-10: L50) is a fairly common syndrome, occurring in 10-20% of the population. Acute urticaria develops quickly and, unlike chronic urticaria, lasts no more than 6 weeks. Urticaria is characterized by clearly defined itchy blisters ranging in size from several mm to several cm with any localization. With generalized urticaria, headache, malaise, arthralgia, fever, abdominal pain, and dyspeptic disorders may be observed. The development of heart failure is possible (especially with severe manifestations of urticaria).
Quincke's edema (ICD-10: T78.3) is characterized by swelling of the skin (dermis and subcutaneous tissue) and mucous membranes. Develops acutely. The swelling is painless. The most typical localization: face, hands, feet, lips, oral mucosa, soft palate, tongue, genitals.
The causes of acute urticaria and Quincke's edema are presented in Table 3.
Basic rules for the treatment of acute urticaria and Quincke's edema.
It is necessary to find out the cause of the disease and try to exclude it. It is recommended to take a large amount of fluid, a cleansing enema, enterosorbents (Enterosgel, activated carbon, Polyphepam, etc.), antihistamines of the old and new generation. Of the old generation H1 blockers, a 2.5% solution of Suprastin or a 0.1% solution of Tavegil is used intramuscularly or intravenously, the daily dose of which is divided into several doses. The duration of parenteral treatment is 5-7 days. Then you can prescribe one of the new generation drugs - Loratadine, Desloratadine, Fexofenadine, Cyterizine.
Glucocorticosteroids (prednisolone 2 mg/kg) - according to indications, especially in case of severe generalized manifestations and ineffectiveness of antihistamines.
For laryngeal edema, parenteral administration of prednisolone 2 mg/kg and hospitalization in the intensive care unit.
Bronchial asthma
Among the emergency conditions that arise during bronchial asthma, there is an exacerbation period and an asthmatic state.
The period of exacerbation of bronchial asthma is characterized by acutely developing bronchial obstruction. In this case, expiratory shortness of breath appears, retraction of the intercostal spaces during inspiration, participation of auxiliary muscles in the act of breathing, noisy, wheezing breathing, wheezing in the lungs. In young children, an acute period of bronchial asthma is accompanied by swelling of the bronchial mucosa with the release of liquid secretion into the lumen of the bronchi, and therefore they can hear both dry and moist wheezing. In young children, observation provides more information about airway obstruction. Symptoms of airway obstruction include signs of increased work of the respiratory muscles (retraction of yielding points, participation of auxiliary muscles, flaring of the wings of the nose), weakening of respiratory sounds, prolongation of the expiratory phase, whistling noises.
In older children, an attack of bronchial asthma is accompanied by a spasm of smooth muscles, and dry wheezing is heard at the height of the attack.
The severity of bronchial obstruction determines the severity of the acute period of bronchial asthma. There are mild, moderate and severe attacks of bronchial asthma and status asthmaticus.
Mild attack
characterized by slight difficulty breathing. Shortness of breath may be absent, the general condition is practically unchanged. When examining the patient, a slight boxy tint to the percussion sound is noted. Hard breathing and a moderate amount of dry rales are heard in the lungs. Accessory muscles are not involved in the act of breathing.
Moderate attack
bronchial asthma, suffocation, disruption of the child’s general condition, exhalation is difficult, the child tries to take a forced sitting position. Accessory muscles are involved in the act of breathing. Cyanosis, a large number of dry whistling and moist rales are heard. There may be tachycardia, a drop in blood pressure.
Severe attack
– severe suffocation, cyanosis of the nasolabial triangle, ears, fingertips. Anxiety, a feeling of fear in a child. There are dry wheezes in the lungs when inhaling and exhaling.
It is very important to distinguish a severe attack of bronchial asthma from the onset of an asthmatic condition.
Asthmatic condition
characterized by the following features:
- intractable attack of bronchial asthma for more than 6 hours;
- resistance to symptomatic therapy;
- development of hypoxemia (PaO22 > 60 mm Hg);
- difficult sputum discharge and the appearance of “silent” zones of the lungs;
- development of dehydration and hypovolemia.
The basis of the asthmatic condition is pronounced bronchospasm, swelling of the bronchial mucosa and hypersecretion, blockade of adrenergic receptors of the bronchial tree, hypercapnia and hypoxia.
To diagnose an asthmatic condition, attention should be paid to physical activity, speech, consciousness, respiratory rate, cardiovascular rate, accessory muscle involvement, and respiration to auscultation.
The concepts of “life-threatening bronchial asthma” are close to the asthmatic condition.
Stages of intensive therapy for the acute period of bronchial asthma.
The child must be reassured and a calm environment created at home or in the hospital.
Rescue medications for asthma include short-acting bronchodilators, which relieve bronchospasm and associated symptoms such as cough, chest tightness, and wheezing.
Treatment begins with the appointment of aerosols of salbutamol or ipratropium bromide in combination with fenoterol. In Russia, an original dosage form (Salgim) was created based on salbutamol, which in its pharmacological properties corresponds to modern β2-agonists.
Administration of drugs for moderate and severe attacks of bronchial asthma is preferable through a nebulizer.
Advantages of nebulizer administration of drugs:
- the inhalation technique is easily feasible for children and elderly patients;
- rapid relief of asthma attacks;
- short treatment time;
- creating an aerosol with an optimal particle size;
- the ability to deliver high doses of the drug directly to the lungs;
- absence of freon and other propellants;
- simplicity and ease of use.
To assess the degree of airway obstruction in a child with an acute attack of bronchial asthma, the PEF (peak expiratory flow) indicator is most often used using a peak flow meter. The advantages of this method include the ease of the procedure, low cost, and the ability to monitor dynamics during therapy. However, the test results are dependent on force and cannot be assessed in young children.
In addition, PSV reflects the function of the bronchi of medium and large diameter, while in asthma the pathological process affects the bronchi of medium and small diameter more. A decrease in PEF to 80% of the calculated norm corresponds to a mild degree of the disease, to 50-80% - to moderate severity, less than 50% means to a severe degree of the disease.
Tactics of administration of patients with exacerbations of bronchial asthma at the outpatient stage.
Initial therapy
: inhaled rapid-acting β2-agonists up to 3 times per 1 hour.
If the answer is good
: PEF exceeds 80%, the effect on the β2-agonist persists for 4 hours. In such cases, the use of the β2-agonist can be continued every 30-40 minutes. within 24-48 hours and correction of planned therapy.
In case of incomplete answer
or moderate exacerbation: PEF 60-80%, it is necessary to add an inhaled glucocorticosteroid (budesonide suspension for nebulizer) or add an inhaled anticholinergic drug, continue therapy, hospitalization is possible.
If the answer is bad
or severe exacerbation: PSV
In recent years, nebulized budesonide (Pulmicort) has been used to relieve moderate and severe attacks of bronchial asthma. It can be used in combination with bronchospasmolytic and mucolytic agents.
Budesonide, an inhaled corticosteroid, in recommended doses has an anti-inflammatory effect in the bronchi, reducing the severity of bronchial mucosal edema, mucus production, sputum production and bronchial hyperreactivity.
Inhaled budesonide is rapidly absorbed. The maximum concentration in blood plasma is reached after 30 minutes. after the start of inhalation.
Drug metabolism and distribution
. Plasma protein binding averages 90%. The volume of distribution of budesonide is 3 l/kg. After absorption, budesonide undergoes intense biotransformation (more than 90%) in the liver with the formation of metabolites with low glucocorticosteroid activity.
Removal
. Metabolites are excreted unchanged in urine or in conjugated form. Budesonide has a high systemic clearance (about 1.2 l/min). The pharmacokinetics of budesonide is proportional to the administered dose of the drug.
Directions for use and doses
. The dose of the drug is selected individually (Table 4). If the recommended dose does not exceed 1 mg/day, the entire dose of the drug can be used at a time (one time). If you take a higher dose, it is recommended to divide it into two doses.
The recommended starting dose for children 6 months and older is 0.25-0.5 mg/day. If necessary, the dose can be increased to 1 mg/day. The dose for maintenance treatment is 0.25-2 mg/day.
It is advisable to determine the minimum effective maintenance dose for all patients.
If it is necessary to achieve an additional therapeutic effect, it can be recommended, due to the lower risk of developing systemic effects, to increase the daily dose (up to 1 mg/day) of Pulmicort instead of combining the drug with oral glucocorticosteroids.
In a life-threatening condition: Euphylline IV 5 mg/kg over 20 minutes, then 1 mg/kg/day (for those who have not received Theophylline orally); Hydrocortisone 100 mg or another steroid at an equivalent dose IV every 6 hours plus Oral Prednisolone 1-2 mg/kg; add ipratropium bromide 0.25 mg to b2-agonists.
Improvement: oxygen through mask; Pulmicort suspension via nebulizer or Prednisolone orally 1-2 mg/kg; b2-agonists via nebulizer often (up to 1 time every 30 minutes); ipratropium bromide via nebulizer every 6 hours.
Progressive hypoxemia is the main cause of death in bronchial asthma. Therefore, the administration of oxygen is the first and necessary step of therapy, and it is also necessary to maintain blood saturation SaO2 within 90-92%.
If there is no improvement, Eufillin IV 1 mg/kg per hour is necessary (monitoring concentrations during infusion for more than 24 hours), as well as transfer to the intensive care unit, if PEF and PaO2 fall and PaCO2 increases, consciousness is impaired, the lung is “silent”.
Thus, knowledge of modern medications and tactics for managing patients with acute conditions of allergic diseases allows us to reliably control these situations.
