Cardiac glycoside and related drug poisoning: clinical guidelines

List of Abbreviations

Terms and Definitions

Myocardial automaticity – the ability of the heart to rhythmically excite and contract without external stimulation, under the influence of impulses originating within the heart itself.

Bathmotropic effect – change in the excitability of various cardiac structures.

Bradyarrhythmias – a group of cardiac rhythm and conduction disorders characterized by slowed generation of electrical impulses, regular or irregular, and slowed ventricular rhythm associated with impulse conduction block.

Myocardial excitability – the property of the myocardium to respond to various external and internal stimuli by transitioning from a resting state to a state of active function.

Secondary nonspecific cardiotoxic effect – clinical manifestations of a disease developing due to toxic myocardial dystrophy in the somatogenic stage of poisoning.

Hypopotassemia – a decrease in the concentration of potassium in the extracellular fluid, which leads to a decrease in cell membrane polarization.

Glycosides – organic compounds whose molecules consist of two parts: a carbohydrate (pyranoside or furanoside) residue and a non-carbohydrate fragment (aglycone).

Deep tendon reflexes – depending on the site where the reflex is elicited (reflexogenic zone), all unconditioned reflexes are subdivided into superficial and deep, distant and those from internal organs. Deep reflexes include tendon, periosteal, and joint reflexes.

Detoxification is the process of neutralizing and eliminating an exogenous toxic substance from the body. Detoxification, as a natural defense process of the body against a toxicant, includes various mechanisms aimed at converting the poison into non-toxic compounds (metabolites), carried out predominantly in the liver, and eliminating the poison or its metabolites via various pathways through the kidneys, intestines, liver, lungs, and skin. During natural detoxification, metabolites more toxic than the ingested toxicant may form (lethal synthesis); furthermore, undergoing metabolism in the liver and excretion through the kidneys, the toxicant and its toxic metabolites can lead to damage to these organs and the development of acute renal or hepatic failure.

Sinus node dysfunction – a condition where the atrial contraction rate does not correspond to physiological needs.

Dromotropic effect – a change in the speed of excitation conduction through the atrioventricular node.

Ventricular rhythm disorders or ventricular tachyarrhythmia – a generalized term for cardiac rhythm disorders in which the source of ectopic activity or the re-entry circuit is located below the bundle of His (in its branches), the Purkinje network, or in the ventricular myocardium.

Idiosyncrasy – a genetically predetermined pathological hyperreaction to specific substances that develops upon the very first contact with the irritant. The condition arises as a result of enzymopathies and is predominantly associated with drug intake.

Inotropic effect – an increase in the force of cardiac contraction.

QT interval – reflects the electrical systole of the ventricles (the time in milliseconds from the beginning of the QRS complex to the end of the T wave). Its duration depends on sex (QT is longer in women), age (QT prolongs with age), and heart rate (HR) (inversely proportional). For an objective assessment of the QT interval, the corrected (adjusted for heart rate) QT interval (QTc) is currently used, determined by Bazett's and Fridericia's formulas. Normally, the QTc is 340-450 ms for women and 340-430 ms for men. A value greater than 500 ms is considered pathological.

Cognitive impairment – a decrease in memory, mental performance, and other cognitive functions compared to the baseline level (individual norm).

Micro- and macropsia – micropsia (parts of one's own body and surrounding objects appear smaller than they actually are); macropsia (objects appear larger to a person, and they appear smaller than in reality).

Arrhythmia – a disruption of the normal physiological sequence of cardiac contractions.

Conduction disorder – a disruption in the propagation of the electrical impulse through the nerve pathways within the atria and ventricles.

Poisoning – a disease developing as a result of external (exogenous) exposure of a human or animal body to chemical compounds in amounts that cause disorders of physiological functions and pose a threat to life.

Paroxysmal atrial fibrillation – a self-terminating cardiac rhythm disorder, in most cases within 48 hours.

Primary cardiotoxic effect / selective myocardial toxicity – the direct action of a poison on chronotropic, dromotropic, and inotropic functions, as well as on vascular tone, arising as a result of impaired cell membrane permeability for electrolytes or altered neurohumoral regulation of myocardial functions.

Polymorphic ventricular tachycardia – unstable, changing configuration of QRS complexes.

Polarization fluorescence immunoassay – a homogenous immunochemical method for determining substances using a fluorescent label, based on the competition between the substance to be determined and a tracer (a low-molecular-weight substance, antigen, labeled with a fluorophore) for binding to specific antibodies and determining the fluorescence polarization of the tracer within the immune complex.

Atrioventricular block – partial or complete interruption of impulse conduction from the atria to the ventricles.

Myocardial conductivity – the ability of the heart to conduct impulses from the site of their origin to other parts of the myocardium.

Psychoactive substance – any substance (or mixture of substances) of natural or artificial origin that affects the functioning of the central nervous system, leading to an altered mental state.

Working group on the development/updating of clinical guidelines – a team of specialists working together and in a coordinated manner to develop/update clinical guidelines and bearing joint responsibility for the results of this work.

Plant poisons – toxic substances contained in plants.

Myocardial refractoriness – a temporary state of tissue inexcitability during the action potential. There are three levels of refractoriness: absolute, effective, and relative refractory periods. The refractory period of atrial cells is shorter than that of ventricular myocardial cells, so the atrial rate can significantly exceed the ventricular rate during tachyarrhythmias. The absolute refractory period lasts no more than 0.1 s and coincides in time with the QRS complex on the ECG. The duration of the absolute and relative refractory periods is about 0.4 s (depending on the heart rate), corresponding to the duration of electrical systole.

Cardiac glycosides – substances of plant origin that exhibit a pronounced cardiotonic effect at therapeutic doses, exert an antiarrhythmic effect, and are used in the treatment of heart failure associated with myocardial dystrophy of various etiologies.

Somatogenic stage of poisoning is a period in the course of acute chemical illness beginning after the elimination or destruction of the toxic substance from the body as a residual lesion of the structure and functions of various organs and systems, typically manifested by various somatic and neuropsychiatric complications such as pneumonia, acute renal failure, hepatic failure, toxic polyneuropathy, anemia, and psycho-organic syndrome. In this stage of poisoning, specific (antidote) therapy is not required, and detoxification may be aimed solely at treating endotoxicosis.

Condition is an alteration of the organism arising from the impact of pathogenic and/or physiological factors that requires medical care.

Toxicogenic stage of poisoning is a period in the course of acute chemical illness beginning from the moment the toxic substance enters the body in a concentration capable of causing a specific effect and lasting until its elimination. It is characterized by specific clinical manifestations reflecting the chemical and toxicological properties of the toxic substance and its effect on target organs. The severity of this disease period directly depends on the dose of ingested poison and its concentration in the blood. The main therapeutic goal in this period is to shorten its duration as early as possible using various methods of accelerated detoxification, antidote, and symptomatic therapy.

Toxicodynamics – a branch of toxicology that studies and examines the mechanism of toxic action, the patterns of development, and the manifestations of various forms of the toxic process.

Toxicokinetics – a branch of toxicology that studies the patterns of entry, absorption, distribution, biotransformation, and excretion of toxicants in the body.

Ventricular flutter – rhythmic, high-amplitude, widened electrical ventricular deflections at a rate exceeding 250 bpm, with T waves being indistinguishable.

Atrial flutter – a supraventricular tachyarrhythmia characterized by atrial excitation at a rate of 250-350 per minute ("flutter waves" with no isoelectric line on the ECG) due to a macro re-entry process around a specific anatomical or functional obstacle (usually involving the tricuspid valve).

Ventricular fibrillation – chaotic electrical activity presenting as polymorphic oscillations that constantly vary in configuration, amplitude, duration, and frequency, with a range of 300 beats/min or higher.

Atrial fibrillation – the most common type of supraventricular tachyarrhythmia with chaotic electrical activity of the atria at a rate of 350-700 per minute (with the absence of a P wave on the ECG), precluding the possibility of their coordinated contraction, and, as a rule, an irregular ventricular rhythm.

Cholinergic syndrome – the syndrome is based on an absolute or relative decrease in cholinergic activity caused by the intake of substances with anticholinergic (cholinolytic) properties.

Cholinomimetics – substances that mimic the effect of acetylcholine by stimulating cholinergic receptors and possess activity similar to it.

Cholinomimetics – medicinal products possessing the ability to produce effects similar to acetylcholine in organs receiving parasympathetic innervation.

Chronotropic effect – a change in the frequency of rhythmic contractions (change in automaticity) of the heart.

Therapeutic width – the range between the threshold and minimum toxic doses. The greater the therapeutic width of a medicinal substance, the greater its pharmacological value, as it facilitates the selection of the optimal dose for each patient and reduces the likelihood of developing toxic effects.

Poisonous plants are plants that produce and accumulate toxic substances causing poisoning in humans and animals.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Acute poisoning by cardiac glycosides and drugs of similar action (according to the ICD-10 formulation) implies a health disorder caused by the entry into the human body of substances belonging to the group of cardiac glycosides and treated as acute poisoning.

Acute poisoning by cardiac glycosides and drugs of similar action, according to the ICD-10 classification (T46.0), is classified as adverse effects resulting from the introduction of cardiac glycosides and drugs of similar action into the human body. This refers to chemical substances contained in medicinal products. Since this nosological group of diseases (T46.0) represents cardiac glycosides and drugs of similar action, for specialists to understand which group the drug belongs to, and consequently to establish a diagnosis and make further decisions on the tactics of medical care, we present the medicinal products according to the Anatomical Therapeutic Chemical classification (ATC classification).

Drug groups by ATC classification.

C01 – Cardiac therapy

Cardiac glycosides (C01A)

Digitalis glycosides (C01AA)

Acetyldigitoxin (C01AA01)

Acetyldigoxin (C01AA02)

Digitalis glycosides, total (C01AA03)

Digitoxin (C01AA04)

Digoxin (C01AA05)

Lanatoside C (C01AA06)

Deslanoside (C01AA07)

Methyldigoxin (C01AA08)

Gitoformate (C01AA09)

Acetyldigoxin in combinations with other drugs (C01AA52)

Squill glycosides (C01AB)

Proscillaridin (C01AB01)

Proscillaridin in combination with other agents (C01AB51)

Strophanthus glycosides (C01AC)

G-strophanthin (C01AC01) – Ouabain

Cymarin (C01AC03)

Other cardiac glycosides (C01AX)

Pharmacological group – Cardiac glycosides and non-glycoside cardiotonic agents:

Peruvoside (C01AX02) – contains cardiac glycosides found in plants of the genus Cascabela thevetia (Thevetia neriifolia);

Corglycard and Corglycon (glycoside from leaves of Convallaria majalis) – active substance Corglycon, dosage 0.6 mg in 1 ml of solution (administered intravenously);

Adonisid concentrated – as of 2024, not listed in the State Register of Medicinal Products;

Adonis-brom (Adonis-Brom; pharmaceutical dosage form: tablets containing thick adonis extract – 0.06907 g, with a total cardiac glycoside content calculated as cymarin and absolutely dry substance of 0.56%, potassium bromide – 0.25 g);

Methyldigoxin (synonyms: Medilasid, Bemekor, Lanitop) – semisynthetic derivative of digoxin;

Pharmacological group – Cardiac glycosides and non-glycoside cardiotonic agents in combinations:

Cardiovalen (adonisid, liquid hawthorn extract, valerian tincture, liquid wallflower herb extract, racemic camphor, sodium bromide);

Cardiotron – herbal preparation, per 100 ml of solution: Lily of the valley tincture 10 ml; Liquid hawthorn extract 30 ml; Liquid nettle extract 60 ml;

Convallaria-Valerian drops;

Valerian rhizomes with roots tincture + Lily of the valley herb tincture (Valerianae officinalis rhizomatum cum radicibus tinctura + Convallariae herbae tinctura);

Convallaria-Motherwort drops;

Hawthorn fruit extract + Stinging nettle leaf extract + Lily of the valley herb tincture (Crataegi fructuum extract + Urticae foliorum extract + Convallariae herbae tinctura).

Non-glycoside cardiotonic agents

Levosimendan.

Plants containing cardiac glycosides are used in pharmaceutical production, folk medicine, and self-medication [1, 2, 3, 4].

Pharmacognosy distinguishes 2 groups of cardiac glycosides [1]: cardenolides and bufadienolides.

Group I – cardenolides.

Purple foxglove (Digitalis purpurea) – type species of the genus Digitalis from the family Plantaginaceae (or Scrophulariaceae) (Digitalis grandiflora, D. lanata, D. ferruginea, D. ciliata; the plant genus Digitalis includes 36 species), contains cardenolides – cardiac glycosides (secondary glycosides: digitoxin, gitoxin, gitaloxin, etc.) from which digitoxin and digoxin are obtained [1, 4].

Oleander (Nerium oleander) – Apocynaceae family; the leaves contain the cardiac glycoside oleandrin (nerifolin, thevetin A, thevetin B). Oleandrin shares properties similar to digoxin, though its effects are less pronounced [1, 4]. Yellow oleander is used in many countries [5].

Yellow oleander (Thevetia peruviana) / Cascabela thevetia – a plant related to Nerium oleander, which gave it the common name yellow oleander [4]. The plant contains cardenolides called thevetin A and thevetin B; others include peruvoside, neriifolin, thevetoxin, and ruvoside.

Greek silk vine (Periploca graeca) – belongs to the Apocynaceae (formerly Asclepiadaceae) family; the bark contains the cardiac glycoside periplocin.

Strophanthus (Strophanthus) – seeds of the following species are used: Strophanthus kombé, S. hispidus, S. gratus, belonging to the Apocynaceae family and containing: K-strophanthoside, K-strophanthin-β, cymarin, K-strophanthidin. The seeds of Strophanthus gratus contain ouabain (g-strophanthin).

Common acokanthera (Acokanthera schimperi) – belongs to the Apocynaceae family. It contains the cardiac glycoside ouabain (g-strophanthin).

Cerbera odollam (Cerbera odollam) – belongs to a species of trees in the Apocynaceae family. The plant's fruits contain the cardiac glycoside cerberin. A single seed contains a lethal dose of the toxin.

Acokanthera (Acokanthera) – contains ouabain (identical to G-strophanthin).

Desert rose (Adenium obesum / Adenium Honghel) – belongs to the Apocynaceae family and contains cardiac glycosides.

Indian hemp (Apocynum cannabinum) – belongs to the Apocynaceae family and contains cardiac glycosides: cymarin and K-strophanthin-β.

Pheasant's eye, or yellow adonis (Adonis vernalis) – a genus of plants in the Ranunculaceae family, containing derivatives of strophanthidin, adonitoxigenin, adonitoxol, and strophadogenin.

Lily of the valley (Convallaria majalis) – contains 20 digitalis-strophanthus-active glycosides (convallatoxin). Caucasian lily of the valley and Keiske's lily of the valley are also used. Belongs to the Asparagaceae family. Medicinal product – Corglycon.

Nalta jute (Corchorus olitorius) – contains cardiac glycosides: olitoroside and corchoroside (close in action to strophanthin).

Diffuse wallflower (Erysimum diffusum), grey wallflower (Erysimum canescens), and treacle mustard (Erysimum cheiranthoides) – plant species of the genus Erysimum, Brassicaceae family. Contain cardiac glycosides: erysimin, pharmacologically similar to strophanthin.

Group II – bufadienolides (combine the positive cardiac effects of digitalis and strophanthus preparations in their pharmacological action).

Caucasian hellebore (Helleborus caucasicus), reddish hellebore (Helleborus purpurascens) – plant species of the Ranunculaceae family. Contain the glycosides corelborin-K and corelborin-P. The drug Corelborin exhibits cumulative effects similar to digitalis preparations; corelborin-P is less toxic than corelborin-K.

Mediterranean squill (Drimia maritima; two varieties are distinguished – white and red) – a plant species of the genus Drimia, containing glycosides: in the white variety – scillaren A and proscillaridin A (scillaren B), and in the red variety – scilliroside. Aqueous infusions are used for cardiac conditions to enhance diuresis (imported).

Climbing bowiea (Bowiea volubilis) and Bowiea kilimandscharica (Bowiea kilimandscharica) – a genus of monocotyledonous flowering plants from the Asparagaceae family containing cardiac glycosides. Also known as sea cucumber, creeping bulb, or climbing onion. The action of glycosides present in the bulbs is 30 times stronger than that of digitalis glycosides, and those contained in the flowers are 60 times stronger [6].

Bufadienolides are also found in toad venom – Chinese toad (Bufo gargarizans / Chan Su) [4].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Advances in studying the pharmacokinetics of cardiac glycosides, mechanisms of their interaction with other drugs, and the use of lower dosages (shifting from serum concentrations considered "therapeutic" for many years in the range of 0.5–2.0 ng/mL to a plasma digoxin concentration of < 0.9 ng/mL; regulated use in patients with heart failure [7] with sinus rhythm or atrial fibrillation at an optimal plasma digoxin concentration of no more than 1.1 ng/mL, corresponding to a dose of 0.25 mg/day) based on serum concentration monitoring [8, 9, 10, 11, 12, 13, 14, 15, 16], as well as the use of digoxin-specific antibody Fab fragments (abroad only), have significantly reduced the incidence of adverse effects and digitalis intoxication [17, 18, 19, 20]. At the same time, cardiac glycosides continue to hold one of the leading places among other drugs in terms of frequency and severity of side effects [21, 22, 23, 24]. In M.J. Ellenhorn's publication (2003), Chapter 74 lists oleander (Nerium oleander) and purple foxglove (Digitalis purpurea) first among plants capable of causing severe acute poisoning [4]. The main causes of poisoning by cardiac glycosides and similar agents are non-compliance with therapeutic dosages, accidental ingestion, suicide attempts, and the accidental ingestion of homemade plant infusions and tinctures [4, 25, 26, 27, 28, 29]. Elderly patients have a high risk of poisoning due to age-related impairments in absorption and elimination, and interactions with other medications they are taking. Drug-drug interactions in elderly patients can alter hepatic and renal clearance and plasma protein binding, thereby affecting bioavailability [29]. It should be noted that cardiac glycosides are also present in the secretion of the cane toad (Bufo marinus) [4].

1.2.1. Toxicokinetics of cardiac glycosides and related drugs

Aglycones (genins) of cardiac glycosides are derivatives of cyclopentanoperhydrophenanthrene [1].

The pharmacokinetics of cardiac glycosides depend on the degree of polarization of their molecules, as well as their water and lipid solubility. By degree of solubility, the glycosides can be arranged in the following order: digitoxin > cymarin > medilazid > digoxin > celanide > strophanthin > convallatoxin.

Main pharmacokinetic parameters of cardiac glycosides. The absorption of lipid-soluble cardiac glycosides (digitoxin, cymarin, medilazid) from the gastrointestinal tract is 60–100%, with peak plasma concentrations reached within 45–60 minutes. Under conditions of increased gastric juice acidity, glycosides are degraded. In blood plasma, glycosides may bind to albumins or circulate in a free state. The clinical effects of cardiac glycosides depend on their average serum concentration, which is determined by the rates of absorption, distribution, and elimination [29].

Polar glycosides exhibit virtually no plasma protein binding (digoxin, cymarin, and medilazid bind by 25%), whereas non-polar glycosides (digitoxin) are almost entirely protein-bound. The pharmacokinetic properties of the primary cardiac glycosides used in medical practice—digoxin and digitoxin—are presented in Table 1.

Table 1 – Pharmacokinetic properties of the primary cardiac glycosides used in medical practice: digoxin and digitoxin (adapted from R. Hoffmann et al., 2010, with additions by B.B. Yatsinyuk et al., 2025) [29].

Note: * – given the time frame presented in the table, it should be noted that if 6 hours have passed since the oral ingestion of a toxic drug dose and a physical examination of the patient reveals no clinical signs of poisoning, further clinical toxicity is unlikely; ** – the specified concentrations are cited from – [30, 31, 32, 33].

The majority of digitoxin is not metabolized during its 'first pass' through the liver and is excreted via bile into the intestine, where it is reabsorbed and returned to the liver. This enterohepatic recirculation continues until free digitoxin is fully converted into metabolites, which are eliminated from the body via urine. Approximately 14% of the total body content is eliminated daily. Excretion and metabolism are independent of liver and kidney function. Due to its high bioavailability and low elimination rate, digitoxin accumulates rapidly [1]. Substances derived from Nerium oleander, Apocynum cannabinum, and Apocynum venetum do not exhibit pronounced cumulative properties. Substances (olitoroside and korchoroside) found in Corchorus olitorius and Erysimum cheiranthoides do not possess cumulative properties.

Digitoxin is almost completely hydrolyzed in the liver and excreted as metabolites. The elimination of celanide and medilazid occurs via the kidneys. Cardiac glycosides have a narrow therapeutic index (narrow therapeutic window), which predisposes patients to adverse pharmacological effects (overdose; poisoning) [16, 24, 34]. Concomitant administration of antibiotics (macrolides) inhibits digoxin metabolism, thereby increasing its bioavailability [29].

The half-life, maximum daily dose, and maintenance dose of the medicinal products are presented in Table 2.

Table 2 – Half-life, maximum daily dose, and maintenance dose of medicinal products [28, 29]

Note: T_1/2 – half-life (depends on renal function); C_max – maximal daily dose; MD – maintenance dose.

1.2.2. Toxicodynamics. Mechanism of cardiotoxic action

The mechanism of action of glycosides is associated (60% or more) with the inhibition of membrane Na⁺/K⁺-ATPase function in the heart, brain, and other organs. Hypokalemia potentiates the effects of glycosides, which additionally suppresses Na⁺/K⁺-ATPase activity. Glycosides exhibit inhibitory activity on the Na⁺/K⁺-pump in the myocardium. Toxic doses of cardiac glycosides disrupt the removal of Na⁺ from the cell and the return of K⁺which exited the cell during membrane repolarization. The main cause of the potassium deficit dependency on magnesium deficiency is considered to be the malfunction of the sodium-potassium pump without Mg²⁺ ions (Mg²⁺-dependent Na⁺/K⁺-ATPase), which accumulates potassium inside the cell. Hypohypokalemia leads to a decrease in cell membrane polarization (this is also facilitated by Na⁺ retention inside the cell). Since the resting potential is lower than normal, during excitation the amplitude of the action potential is also reduced, thereby disrupting the coupling process of membrane action potential changes with myofibril contraction. The membrane Na⁺/K⁺-ATPase of various cells in the heart has unequal affinity for glycosides. Furthermore, the ATPase of cell membranes in the cardiac conduction system is 2.5 times more sensitive than the myocardial myocyte enzyme. This causes a negative dromotropic effect, and due to increased vagal tone, conduction in the atrioventricular node is impaired [5, 27, 29].

Toxic concentrations of cardiac glycosides promote the release of acetylcholine. Due to the inhibition of Na⁺/K⁺-ATPase in biomembranes, the Na⁺/K⁺ ratio changes, which facilitates the influx of Ca²⁺ (accumulation of Ca²⁺ in cardiomyocytes leads to delayed afterdepolarizations, resulting in extrasystole and ventricular tachycardia) into cells in exchange for Na⁺. As a result of these changes, spontaneous depolarization occurs in Purkinje fibers, contributing to the appearance of ectopic foci of excitation in the ventricles and extrasystole. Toxic doses of cardiac glycosides increase the activity of the parasympathetic system (vagus nerve), promote the release of acetylcholine from cholinergic nerve endings in the heart, thereby enhancing the reflex from baro- and chemoreceptors, which leads to bradycardia, conduction disturbances, atrioventricular blocks, and asystole [27, 29]. Cardiac signs of acute cardiac glycoside poisoning are presented in Table 3.

Table 3 – Cardiac signs of acute cardiac glycoside poisoning according to V.V. Afanasyev (2009) [35]

The toxic effect of cardiac glycosides is caused by excessive inhibition of Na⁺/K⁺-ATPase, which accumulates calcium inside the cell ("calcium overload of the cell" causes ventricular fibrillation), and "spontaneous" release of calcium from the sarcoplasmic reticulum, which serves as a trigger for delayed post-depolarization and cardiac arrhythmias, which are the leading cardiac disorders [24, 25, 26, 28, 36].

Hypokalemia potentiates the toxic pharmacological effects of cardiac glycosides, leading to more pronounced rhythm disturbances at lower serum concentrations. The occurrence of hypokalemia is facilitated by the use of loop diuretics, insufficient intake into the body, and elimination from the body as a result of diarrhea.

1.2.3. Pathogenesis of gastrointestinal disorders

Gastrointestinal syndrome is associated with reflex excitation of the vomiting center (located in the medulla oblongata, lower part of the floor of the 4th ventricle) by cardiac glycosides. In some cases, nausea and vomiting may be due to idiosyncrasy to cardiac glycosides. The frequency of gastrointestinal syndrome varies from 11% to 40% and may be the sole syndrome of intoxication. With oral administration of cardiac glycosides, gastrointestinal syndrome (when taking Digitalis purpurea, preparations, vomiting occurs within 1-3 hours) is caused by the irritating effect of glycosides on the mucous membranes of the gastrointestinal tract. Acute poisonings with Nerium oleander resemble digoxin poisoning and include nausea and vomiting that occur several hours after toxicant ingestion [4].

1.2.4. Pathogenesis of cholinomimetic syndrome

Cholinomimetics are drugs that have the ability to produce effects similar to acetylcholine in organs receiving parasympathetic innervation. Acetylcholine is characterized by a variety of sites of action and multidirectional resulting effects (visual system, endocrine glands, gastrointestinal tract, bronchi, heart). Of decisive importance in the development of clinical manifestations is the selectivity of the action of cholinergic agents on cholinoceptors. There are two main types of cholinoceptors – muscarinic, or M-cholinoceptors, and nicotinic, or N-cholinoceptors. M-cholinoceptors are localized predominantly in central nervous system cells, the heart, glands, and endothelium, whereas N-cholinoceptors are localized in neuromuscular junctions and nerve ganglia. In view of the foregoing, the pharmacological action of cholinoceptor stimulants is determined by their selectivity, which makes it possible to achieve the desired effects and cause clinical manifestations of poisoning [4, 28, 29].

1.3 Epidemiology of the Disease or Condition

In the Russian Federation, acute poisoning with cardiac glycosides and drugs of similar action is rarely registered. According to reports from the Center for Acute Poisoning of the Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine (Form No. 64 for 2017–2019), patients with this nosological form of the disease accounted for 0.09%, 0.074%, and 0.025% of all hospitalized patients in the Center for Acute Poisoning. According to reporting form No. 64 in the Khanty-Mansi Autonomous Okrug, acute poisoning with cardiac glycosides and drugs of similar action (2022–2023) averaged 0.3% of all poisonings in the region in 2019–2020.

In modern clinical practice, cardiac glycosides are widely used. Chronic heart failure (CHF) and tachyarrhythmias – paroxysmal atrial fibrillation (AF), paroxysmal supraventricular tachycardia – are the main indications for prescribing cardiac glycosides [24, 40]. In cardiac glycoside poisoning, mortality can exceed 2% and is usually due to delayed hospitalization [5].

1.4 Features of Coding the Disease or Condition

Coding of the diagnosis is carried out in accordance with the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). In the ICD-10 revision adapted for Russia, 7 characters are used, which make it possible to formalize the diagnosis of the disorder detected in the patient.

In ICD-10, poisoning by cardiac glycosides and drugs of similar action is considered in section T46 – Poisoning by agents primarily acting on the cardiovascular system.

XIX Injury, poisoning and certain other consequences of external causes (S00–T98):

T46.0 – Poisoning by cardiac glycosides and drugs of similar action.

1.5 Classification of the disease or condition

In the classification of drugs acting on the cardiovascular system, there are the following data on cardiac glycosides used for cardiovascular diseases: group – Cardiotonic agents; subgroup – Cardiac glycosides; drugs: foxglove, pheasant's eye, strophanthus, wallflower in [27].

General characteristics of cardiac glycosides [25, 26, 27].

Classification of cardiac glycosides and drugs of similar action:

Digitalis glycosides: digitoxin, digoxin, lanatoside C, lantoside.

Strophanthus glycosides: strophanthin K.

Adonis glycosides: adoniside, herb infusion.

Convallaria majalis glycosides: corglycon.

Preparations containing glycosides: cordigit, cordalen, lanicor, dilacor, methyldigoxin, celanid, isolanid, adoniside, (Bekhterev's mixture, cardiovalen, corglycon, lily of the valley drops).

In recent decades, the use of cardiac glycosides in clinical practice has decreased significantly, which is associated with a narrow therapeutic window and frequent side effects, on the one hand, and the development of other drugs for the treatment of circulatory failure, on the other.

Glycosides are nitrogen-free compounds of plant origin that have a cardiotonic effect. A cardiac glycoside molecule consists of two parts: a sugar part (glycone) and a non-sugar part (aglycone). The specific cardiotonic effect is primarily due to the aglycone, while glycones affect solubility, drug absorption, permeability, protein-binding capacity, metabolism, elimination, and duration of action, and therefore largely determine the pharmacological properties.

For clinical and diagnostic purposes (to establish a preliminary and clinical diagnosis and determine the management and care tactics), acute poisoning with cardiac glycosides and drugs of similar action (other drugs primarily acting on the cardiovascular system) is divided into three groups according to severity in accordance with the classification of E.A. Luzhnikov (2001) [41]. The classification for assessing the severity of poisoning with drugs primarily acting on the cardiovascular system is presented in Table 4.

Table 4 – Classification for assessing the severity of poisoning with drugs primarily acting on the cardiovascular system (E.A. Luzhnikov, 2001, with additions by B.B. Yatsinyuk et al., 2025) [41].

Note: *polytopic premature beats originate from multiple ectopic foci, with varying coupling intervals on the same ECG lead (differences exceed 0.02-0.04 s), and different morphology of premature complexes; **triggered atrial tachycardia is based on delayed afterdepolarization occurring with increased sympathetic tone or high doses of glycosides.

1.6 Clinical presentation of the disease or condition

Toxic effects – the clinical picture of acute cardiac glycoside poisoning is determined by: the dose of the ingested chemical, specifics of its toxico- and pharmacokinetics and toxic mechanisms, pre-existing chronic heart disease (CHF) in the patient, the severity of hypokalemia (potassium is a cardiac glycoside antagonist), and acidosis, which promotes intracellular potassium loss and thereby worsens the course.

The asymptomatic period after cardiac glycoside ingestion can last from several minutes to several hours [27, 28, 29, 42].

Acute poisoning presents with cardiac and non-cardiac manifestations.

1.6.1. Non-cardiac symptoms

Non-cardiac symptoms of cardiac glycoside poisoning often develop earlier than cardiac ones and are usually clearly described by the patient when taking the medical history. According to M.N.G. Dukes (1980), general and toxic reactions from therapeutic doses of cardiac glycosides are accompanied by anorexia and nausea [43].

Gastrointestinal syndrome – one of the earliest to manifest, accompanied by symptoms related to the chemical's effect on the gastrointestinal tract: mild abdominal pain, nausea, repeated vomiting, and diarrhea [3]. A "wave of nausea" with profuse salivation preceding vomiting is noted [37]. Vomiting may also occur suddenly, without prodromal signs. In some clinical cases, diarrhea may be the first symptom [37]. Abdominal pain may result from intestinal spasm or mesenteric vasoconstriction. Gastrointestinal bleeding [28, 35] and clinical manifestations of hemorrhagic intestinal necrosis are observed in some cases [37]. The severity of dyspeptic symptoms (gastrointestinal syndrome) is directly dependent on the ingested dose [37], the composition of the dosage form [35], or the substance containing the toxic agent [4, 28, 29]. Cerberin poisoning is accompanied by a burning sensation in the oral cavity, while poisoning with climbing bowie (Bowiea volubilis) and Kilimanjaro bowie (Bowiea kilimandscharica) is accompanied by hypersalivation.

Cholinomimetic syndrome. A syndrome developing as a result of chemical substances (cardiac glycosides) acting on organs with parasympathetic innervation, clinically manifested by increased gastrointestinal motility and secretory activity, miosis [35, 38], hyperhidrosis, increased salivary and bronchial gland secretion [35], bradycardia, and AV block [4, 28, 29, 44].

Central nervous system (CNS) dysfunction manifests as: headache, dizziness, and seizures.

Mental status impairment is accompanied by: depressive state, fear, disorientation, hallucinations, delusions, delirium (delirium*, digitalis delirium**) [45]. Predisposing factors for delirium related to cognitive status include dementia, cognitive impairment, and a history of delirium [46].

*Delirium is a mental disorder occurring with impaired consciousness. It is characterized by true hallucinations and illusions (predominantly visual) and secondary delusions; emotional-affective disorders, sensopathies, impaired environmental orientation, and disorientation in time. Personal identity and awareness of danger remain intact. The patient's emotional state depends on the nature of the hallucinations. Recovery from delirium is followed by partial congrade amnesia (real events and painful memories are forgotten). The patient may be dangerous to themselves and others.

**Digitalis delirium is a mental disorder occurring during the toxigenic stage of cardiac glycoside poisoning.

The pathogenetic aspects of delirium are multifactorial, comprising neurotransmission disorders and neurotransmitter imbalance, cell membrane instability, and impaired oxygen delivery and utilization. In these exogenous exposures, delirium is not a manifestation of a primary psychiatric disorder, but rather one of the syndromes of acute poisoning – the exogenous effect of a toxic substance [46, 47].

Aphasia is observed – complete or partial loss of the ability to communicate thoughts through words, write thoughts, and/or understand speech directed at them. Cognitive impairments occur – decreased memory, mental performance, and other cognitive functions [16].

Visual disturbances are possible, characterized by color perception abnormalities (yellow-green color aberrations) [35, 37, 43, 44], transient diplopia (double vision of a single object), decreased visual acuity, and micro- or macropsia.

Hypokaligistia down to 300 mmol may not be accompanied by clinical manifestations; however, as the deficit increases, apathy, drowsiness, agitation, muscle hypotonia, and sluggish peristalsis occur, accompanied by fluid accumulation in the intestinal lumen (fluid accumulation increases potassium loss).

Peripheral nervous system lesions are noted – trigeminal and lumbar neuritis, intercostal neuralgia, paresthesias [37], though they are less specific than cardiac ones.

Rare manifestations of glycoside poisoning include: thrombocytopenic purpura accompanied by increased platelet destruction, elevated prothrombin index, and increased blood coagulation properties [37]. Development of toxic thrombocytopenia [43, 44]. Eosinophilia is noted [43, 44].

Skin lesions

Contact with oleander (*Nerium oleander*) causes dermatitis [48].

1.6.2. Cardiac manifestations of acute poisoning

Due to metabolic disorders in the myocardium, the patient complains of pain in the epigastric region and behind the sternum, sometimes radiating to the back [38].

Cardiac manifestations of cardiac glycoside poisoning include disorders of automaticity, conductivity, excitability of the heart's conduction system, and myocardial refractoriness [4, 5, 28, 29, 35, 37]. Sinus bradycardia is one of the earliest and most typical manifestations of poisoning in adults (Methyldigoxin, Strophanthin G). Slowing of atrial and atrioventricular (AV) conduction may manifest as a trend correlating with the degree of bradycardia. Moderate and severe poisoning present with AV blocks of varying degrees. Second- and third-degree blocks are predictors of tachyarrhythmias and are typical for severe poisoning (Methyldigoxin). Complete AV block is a life-threatening condition. Atrial and ventricular premature beats are observed. Frequent premature beats predispose to more severe forms of arrhythmias. Sinus bradycardia combined with AV block is more characteristically accompanied by bigeminal or trigeminal ventricular ectopy [5, 28, 35]. Poisoning with sea mango (Cerbera odollam) is characterized by bradycardia.

The development of triggered atrial focal tachycardias with a heart rate ranging from 100 to 150-200 bpm is characteristic. P waves are monomorphic and typically positive in leads II, III, and aVF; lower atrial tachycardias with inverted P waves are less common. The atrial rhythm can be either regular or irregular. Alternation of short and long P-P intervals is observed. In digitalis intoxication, focal atrial tachycardia is typically combined with second-degree AV block. The block can develop at an atrial rate of 100-120 bpm and may reach 200 bpm or more. A distinctive feature of this block is that it appears almost from the moment the tachycardia attack begins and is notable for its persistence, since the factors causing ectopic activity and the block are the same. AV block can vary in severity from Wenckebach periodicity (3:2, 4:3) to 2:1 or 4:1 block. In severe digitalis intoxication, ventricular tachycardia progressing to ventricular fibrillation may develop.

Typical ECG manifestations of cardiac glycoside poisoning include: T-wave changes (decreased amplitude, biphasic, T-wave inversion); shortening of the Q-T interval; ST-segment depression (downsloping ST depression progressing to a negative T wave – a characteristic manifestation of cardiac glycoside effects) ranging from moderate to a "scooped-out" shape; prolongation of the R-R and P-Q (P-R) intervals. These changes are most prominent in standard leads II and III, augmented lead aVF, and left precordial leads [28, 29, 35]. Both prolonged and shortened QT intervals increase the risk of life-threatening ventricular arrhythmias.

In poisoning with *Bowiea volubilis* and *Bowiea kilimandscharica*, cardiac symptoms (arrhythmia) occur within a few minutes (depending on the dose taken); cardiac arrest occurs in the diastolic phase [6].

It should be noted that if atrioventricular block is caused, at least in part, by vagal influence, it can be reversed by administering Atropine [5, 29]. With direct glycosidic effects on the AV node (bradyarrhythmias developing in the late period of acute poisoning and in chronic digitalis intoxication), this pharmacological effect is unattainable [4, 29]. Rhythm and conduction disorders identified in cardiac glycoside poisoning are presented in Table 5.

Table 5 – Rhythm and conduction disorders identified in cardiac glycoside poisoning [35, 41, 49]

Taking into account the data presented in Table 5, the main cardiac abnormalities on the ECG are: downsloping ST-segment depression progressing to a negative T wave; prolongation of the P-Q interval [27, 29, 35]. Supraventricular tachyarrhythmias with high AV conduction are not characteristic of cardiac glycoside poisonings [29].

Supraventricular arrhythmias include: premature atrial contractions (PACs); supraventricular tachycardia (SVT); atrial fibrillation (AF).

The duration of the cardiac effects of cardiac glycosides in acute poisoning with *Nerium oleander* lasts up to 3–6 days, with methyldigoxin up to 9 days, and with ouabain intoxication up to 3 days [4, 29].

1.6.3. Water and electrolyte disorders

Hypokaligistia and hypokalemia occur against the background of chronic heart failure, hypoxia, acidosis, and diuretic therapy, and are risk factors that aggravate the course of acute poisoning. Hypomagnesemia, hypercalcemia, hypernatremia, and hypoproteinemia are also considered risk factors [28, 29, 35].

High and low potassium concentrations

The toxicity of cardiac glycosides depends on the blood K⁺ concentration [4, 29, 37].

Hyperkalemia. This disorder is pathogenetically justified in acute poisoning and serves as an important prognostic criterion for the severity of the condition [3, 4, 29]. The degree of hyperkalemia correlates with the probability of a fatal outcome and is an indicator of poisoning severity. However, it is not the direct cause of complications and death [3, 29]. Potassium levels in acute fatal poisonings reported in literature range from 6.6 mEq/L to 8.6 mEq/L [4]. Plasma potassium levels have greater diagnostic value than the ECG and plasma cardiac glycoside concentrations [49].

Hypokalemia. Cardiac glycosides and potassium ions compete for common binding sites on Na⁺/K⁺-ATPase (potassium acts as a cardiac glycoside antagonist). Hypokalemia increases cardiac glycoside binding to the enzyme, thereby enhancing their pharmacological and toxicological activity. When the potassium concentration drops to 1.5 mmol/L, severe rhythm disturbances and ventricular fibrillation may occur at lower serum cardiac glycoside concentrations [16, 28, 37]. Most commonly, this disorder occurs against the background of diuretic therapy in individuals receiving long-term cardiac glycoside therapy [29]. Severe hypokalemia is defined as a serum potassium level of less than 3 mEq/L [50]. Hypokalemia is considered to be a decrease in plasma potassium levels below 3.5 mmol/L [35, 50].

Hypomagnesemia. Under conditions of hypomagnesemia, the antiarrhythmic effect of cardiac glycosides is potentiated, which is important in the development of their cardiotoxic effect [37, 51].

The action of digitalis preparations is based on the inhibition of Mg²⁺-dependent Na⁺/K⁺-ATPase (the sodium-potassium membrane pump) [50]. Clinical signs of hypomagnesemia include: hypokalemia, disorders of neuromuscular excitability, and cardiovascular dysfunction – arrhythmias [50, 52]. In moderate magnesium deficiency, an increase in QRS complex duration and T-wave amplitude is observed, whereas in severe deficiency, there is prolongation of the P-R interval, progressive lengthening of the QRS complex duration, and a decrease in T-wave amplitude [53].

Normal serum magnesium concentration is 1.5–2.0 mEq/L (obtained concentrations must always be correlated with clinical data) [50]. A normal blood magnesium concentration is considered to be in the range of 0.75–0.95 mmol/L (0.7–1 mmol/L) [51, 54, 55].

Given that acute cardiac glycoside poisonings occur predominantly in elderly patients with existing somatic disorders, the cause of hypomagnesemia may be diabetes mellitus, where a correlation between the severity of magnesium deficiency and blood glucose levels has been established [56].

A blood magnesium concentration of less than 0.82 mmol/L with a urinary magnesium excretion ranging from 40–80 mg/day suggests a high probability of magnesium deficiency [57]. A blood magnesium concentration greater than 0.95 mmol/L may indicate hypermagnesemia [51].

1.6.4. Changes in renal and hepatic function

The patient's pre-existing chronic liver disease and renal impairment contribute to alterations in the metabolism and elimination time of the toxic substance, an increase in its plasma concentration, and a decrease in clearance, thereby leading to an increased concentration in the myocardium, which largely determines the development of complications [37]. Heart disease – chronic heart failure – exacerbates liver damage, manifesting as cardiohepatic syndrome (there is a hepatotropic effect of the pathogenetic factors of chronic heart failure on the liver tissue), which alters the metabolism (hydrolysis) of cardiac glycosides in the liver [37, 58, 59, 60, 61, 62, 63].

Changes in the severity of a patient's condition in cardiac glycoside poisoning occur with reduced renal excretory function (increased serum cardiac glycoside concentration), cardiovascular pathology (right ventricular heart failure and other disorders), altered electrolyte levels, hypoxemia and hypercapnia, and the concomitant administration of cardiac glycosides with other medicinal products (specified in subsections 3.2 and 3.3) [16, 25, 26, 27].

1.6.5. Features of cardiac glycoside poisoning in children

According to E.A. Luzhnikov and G.N. Sukhodolova, in acute poisonings with cardiotropic poisons in children, a hyperkinetic type of circulation is determined in the initial period of exotoxic shock as a response of the cardiovascular system to the toxicant. Subsequently, a hypokinetic type prevails [64]. According to R. Hoffman et al. (2010), glycoside intoxication manifests similarly in children and adults [29].

In young children, central nervous system disorders are more pronounced due to a larger volume of distribution compared to adults. Clinically, central nervous system disorders manifest as depressed consciousness or agitation, delirium, and hallucinations. The probability of developing seizure syndrome is higher. Visual disturbances are also observed more frequently. Due to the peculiarities of neural regulation, sinus bradycardia may be absent in children, with only a decrease in heart rate relative to the age-specific norm being detectable.

Peculiarities of diagnosis formulation/establishment based on the clinical manifestations of the disease/condition.

Depending on the clinical symptoms observed, the analysis/interpretation of the obtained laboratory and instrumental test results (ECG and other methods), as well as the dynamics of the patient's condition, a clinical diagnosis is established.

Example of formulating a clinical diagnosis: Severe cardiac glycoside (digoxin) poisoning, toxicogenic stage (T46.0). Toxic cardiomyopathy (I42.7). Ventricular tachycardia (I47.2). Paroxysmal atrial fibrillation (I48.0). Hyperkalemia (E87.5). Toxic encephalopathy with impaired mental functions – digitalis delirium (G92).

It was previously considered incorrect to classify rhythm and conduction disorders developed during the formulation of the diagnosis structure as complications of the primary diagnosis. The detected disorders are a consequence of toxic concentrations, and as shown in Table 4 (Classification for Assessing the Severity of Poisoning), their severity and combination serve as an indicator of the severity of poisoning, which is indicated in the main diagnosis. When formulating the diagnosis structure, clinical guidelines should be used: Bradyarrhythmias and Conduction Disorders, Atrial Fibrillation and Flutter in Adults, Ventricular Arrhythmias. Ventricular Tachycardia and Sudden Cardiac Death, Supraventricular Tachycardias [65, 67, 68, 69].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Medical indications and contraindications for diagnostic methods

Diagnosis must be based on the following diagnostic criteria:

• evidence of the use of chemical substances belonging to cardiac glycosides and drugs with a similar mechanism of action;

• presence of symptoms and signs of toxic effects corresponding to the syndromes and clinical courses of poisoning hazardous to the life and health of patients;

• existing symptoms or signs cannot be explained by a disease unrelated to the use of this group of substances, as well as by other conditions.

2.1 Complaints and Anamnesis

Symptoms in acute poisoning depend on the dose of the ingested chemical substance, chronic heart diseases for which the patient constantly receives cardiac glycosides, the severity of symptoms and syndromes, the period of acute poisoning, and the failure of organ and body systems. Additionally, patient complaints may be caused by the development of complications during the toxicogenic and somatogenic periods of acute poisoning. In the initial period, clinical manifestations may occur with the development of gastrointestinal syndrome without cardiac disorders, or these disorders may be minimal, subsequently dominating over other dysfunctions of the body systems. During the period of pronounced clinical manifestations of the disease, complaints may be absent due to severe functional disorders, primarily of the central nervous system, as contact with the patient is limited [28, 29, 38, 41].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: in cases of cardiac glycoside poisoning, general principles of taking a toxicological history are far from always applicable. This applies to establishing such details as: the type or name of the plant ingested by the victim; the time of their intake (toxin exposure in the body), which allows estimating the time period or stage of poisoning with a certain degree of accuracy (the dose of the ingested toxic substance determining the possibility of acute poisoning and the severity of the disease can only be assumed); circumstances accompanying the development of poisoning (accidental or intentional, most often accidental). Practically none of the above can be ascertained when relatives are absent and the patient cannot report the necessary information due to their condition. In such cases, the diagnosis is established based on the clinical syndrome [25, 26, 27, 28].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: diagnosis of the toxic effect of glycosides is based on medical history data, the dynamics of clinical manifestations in the toxicogenic and somatogenic stages, and instrumental and laboratory test data [26, 27, 28, 49].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

2.2 Physical Examination

Comments: it is necessary to assess impaired respiratory functions (rate, depth, uniform involvement of all chest parts in the breathing act), evaluate the pulmonary auscultation pattern and clinical data corresponding to respiratory failure; the cardiovascular system (pulse examination, heart auscultation, measurement of heart rate, cardiac rhythm, blood pressure); signs of hypovolemia, dyselectrolytemia, and acid-base disorders; signs of liver dysfunction against the background of chronic heart failure, the presence of acute kidney injury, coagulopathy, and gastrointestinal dysfunction. To assess the level of consciousness impairment, and for quantitative assessment of coma severity and neuropsychiatric disorders, it is necessary to use the Glasgow Coma Scale (Appendix G1). To assess the severity of poisoning, it is necessary to use the Poisoning Severity Scale (Appendix G2).

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: assessment of the cardiac effects of toxic doses of cardiac glycosides and drugs with a similar mechanism of action is carried out based on medical history, physical examination, analysis of monitored parameters, and electrocardiographic data analysis) [25, 26, 27, 28, 29, 65, 66, 67, 68, 69].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: it is necessary to perform differential diagnosis with diseases/conditions: acute coronary syndrome (myocardial infarction, unstable angina) [25, 26], infectious gastroenteritis, poisoning with iron salts (Fe²⁺), lithium (salts: lithium carbonate, citrate, oxybutyrate), arsenic (As³⁺, As⁵⁺), antimony; poisonings with plant toxins: Veratrum, Aconitum (aconitine alkaloid), Eleutherococcus/Kalopanax (flavonoglycosides); drug poisonings: antipsychotics (thioridazine, mesoridazine, cyprazone, amantadine), tricyclic antidepressants (amitriptyline, imipramine, desipramine) [28, 35, 49].

When carrying out differential diagnosis measures, it is necessary to consider: the intake of chemical substances, the time elapsed from the start of intake to the first clinical symptoms of the disease, and the duration of the latent period. During differential diagnosis, it should be taken into account that the pathological process resulting from poisoning with cardiac glycosides and drugs of similar action is not characterized by an elevated body temperature [26, 27, 28, 35]. Difficulties in evaluating ECG data may arise in patients chronically receiving cardiac glycosides. In this case, it is necessary to compare previously performed ECG studies and evaluate the existing ECG changes over time [26, 27, 28, 35].

2.3 Laboratory Diagnostics

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comment: quantitative determination of many cardiac glycosides, except for digoxin, does not yet have clinical significance. Most tests for the qualitative determination of digoxin may yield a positive reaction for other cardiac glycosides [29].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comment: the frequency of laboratory testing methods will depend on the severity of the disease/condition and existing complications, and is determined by the attending physician.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comment: intoxication markers: myoglobin in blood and urine, serum potassium, creatine phosphokinase, alanine and aspartate transaminases [70].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: for the purpose of differential diagnosis between the pathological process of toxic hepatopathy and liver disease of viral etiology, perform the following serological tests:

• Determination of hepatitis B virus (Hepatitis B virus) e-antigen (HBeAg) in blood;

• Determination of hepatitis B virus (Hepatitis B virus) surface antigen (HBsAg) in blood;

• Determination of hepatitis C virus (Hepatitis C virus) core antigen in blood;

• Qualitative determination of antibodies to hepatitis B virus (Hepatitis B virus) surface antigen (anti-HBs) in blood;

• Determination of hepatitis B virus (Hepatitis B virus) DNA in blood by PCR, qualitative and quantitative assays;

• Determination of total class M and G antibodies (anti-HCV IgM and anti-HCV IgG) to hepatitis C virus (Hepatitis C virus) in blood;

• Determination of hepatitis C virus (Hepatitis C virus) core antigen in blood;

• Determination of hepatitis C virus (Hepatitis C virus) RNA in blood by PCR, qualitative assay;

• Testing for class M and G antibodies (IgM, IgG) to human immunodeficiency virus HIV-1/2 and antigen p24 (Human immunodeficiency virus HIV 1,2/+Agp24) in blood;

• Determination of human immunodeficiency virus RNA by PCR, qualitative assay.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

2.4 Instrumental Diagnostics

Performing instrumental diagnostic studies helps to clarify the diagnosis of acute poisoning by cardiac glycosides and drugs of similar action. Instrumental examinations are necessary for early diagnosis of disorders in mild, moderate, and severe cases of the disease. These disorders may indicate changes in various organs and systems that require verification and assessment, and they allow for supplementing the options of care provision at its various stages [28, 82, 83, 84, 85].

LCE – 5 GLE – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments. In acute poisoning by cardiac glycosides and drugs of similar action, ECG reveals disorders of myocardial excitability, automatism, conduction, and refractoriness. To establish the diagnosis of atrial fibrillation/atrial flutter, a registered episode of arrhythmia with characteristic ECG features lasting at least 30 seconds is required [65, 66, 67, 68, 69].

If the patient has not previously received cardiac glycosides (for a heart condition), the detected abnormalities — such as decreased amplitude, biphasic and inverted T wave, shortened QT interval, moderate to "scooped-out" ST-segment depression, increased RR and PQ (PR) intervals — should be regarded as a consequence of acute poisoning [35].

It is difficult for a specialist interpreting ECG results to evaluate the data obtained in patients chronically receiving cardiac glycosides. To evaluate such patients, it is necessary to compare previous ECG studies (if available) and assess the changes dynamically [35].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: performing an ultrasound diagnostic method (EchoCG) makes it possible to assess the likelihood of cardiomyopathy, chronic heart disease, and cardiac rhythm and conduction disorders.

Level of Evidence (LoE) – 5, Grade of Recommendation (GoR) – C.

Comments. Vital signs should be monitored instrumentally using a resuscitation cardiac monitor. In the absence of a monitor, vital signs are monitored periodically manually. The frequency of repeated measurements is determined by the attending physician depending on the severity of the patient's condition. Instrumental diagnostic methods are an integral part of the diagnostic process and are performed in a setting where dynamic monitoring of the patient's condition is possible. The inability to perform instrumental monitoring in a severely ill patient requires considering the issue of medical evacuation to a medical organization where this is possible.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

2.5 Other Procedures

Additional diagnostic methods are prescribed by specialists based on the existing clinical situation in accordance with indications. Since acute poisonings with cardiac glycosides and preparations of similar action are accompanied by various disorders in the organs and body systems, have variability in clinical manifestations of the disease and various complications, there is often a need for differential diagnostics and examination of patients by specialist physicians.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. General approaches to the treatment of acute poisoning by cardiac glycosides and preparations of similar action

The severity of clinical manifestations of acute poisoning by cardiac glycosides and preparations of similar action depends on the dose of the ingested chemical substance, the characteristics of their toxico- and pharmacokinetics, and the mechanisms of toxic action. The asymptomatic period after taking cardiac glycosides can last from several minutes to several hours. In the toxicogenic stage of poisoning, cardiac and non-cardiac manifestations of the disease occur.

Non-cardiac manifestations: gastrointestinal syndrome, cholinomimetic syndrome (often developing earlier than cardiac ones), central nervous system dysfunction, peripheral nervous system lesions, thrombocytopenic purpura, toxic thrombocytopenia, eosinophilia, skin lesions — dermatitis. Water-electrolyte disorders: elevated and decreased potassium concentrations, hypomagnesemia.

Cardiac manifestations: disorders of automatism, conduction, excitability of the heart's conduction system, and myocardial refractoriness — sinus bradycardia, AV blocks, tachyarrhythmias, triggered atrial ectopic tachycardias, shortening of the Q-T interval; ST-segment depression, prolongation of the R-R and P-Q (P-R) intervals, and others listed in Table 5. Supraventricular arrhythmias include: atrial extrasystoles (AE); supraventricular tachycardia (SVT); atrial fibrillation (AF).

3.2. Emergency medical care outside a medical facility

At the pre-hospital stage, all patients with acute poisoning by cardiac glycosides and preparations of similar action, following the administration of medications, should be assessed for the development of anaphylaxis and anaphylactic shock, performing all necessary medical techniques and a set of drug administration measures in accordance with clinical guidelines if they occur [87].

When treating all patients, before prescribing drugs from other pharmacological groups, one should review the instruction section on drug-drug interactions in order to prevent the risk of their combined use and avoid increasing the toxic effects of cardiac glycosides; drugs should be prescribed taking into account the instructions for medical use, the patient's age, sex, severity of the disease, presence of complications of the underlying disease (condition), and comorbid conditions (Russian Ministry of Health Order No. 203n) [119].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: this medical technique of gastric lavage helps to reduce the concentration of toxic substances in the gastrointestinal tract and decreases the absorption of ingested toxicants into the blood [28, 29, 49]. Gastric lavage is performed in the absence of life-threatening cardiac arrhythmias in the patient, as this medical procedure may induce a vagal effect, provoking bradycardia, ventricular fibrillation, and asystole (especially in children) [28, 29, 35].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comment: parenteral (intravenous) administration of a medicinal product from group A03F Gastrointestinal motility stimulants A03FA01 #Metoclopramide** — adults 10–20 mg (for intractable vomiting 1–2 mg/kg diluted in 5% dextrose solution**), children 0.1 mg/kg [35, 49, 119].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: in case of hyperkalemia of other etiologies, calcium administration has a good clinical effect; however, in case of cardiac glycoside poisoning, the use of calcium salts is dangerous, since patients already have an elevated intracellular concentration [29] and its administration can lead to toxic effects and ventricular fibrillation [49].

3.3. Treatment at the stage of specialized medical care

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: the need for catheterization of the cubital and other peripheral veins, implantation of a subcutaneous venous port system, catheterization of the subclavian and other central veins is within the competence of the anesthesiologist-intensivist (attending physician) and is determined by the patient's status (severity of the condition), presence of concomitant diseases, and anamnestic data of taking cardiac glycosides and drugs of similar action against the background of chronic heart diseases [27, 28, 37, 44, 49].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

3.3.1. Correction of cardiotoxic manifestations and hemodynamic disorders

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: simultaneous (timed) administration of solutions: group B05BA Solutions for parenteral nutrition – Carbohydrates – B05BA03 #Dextrose** (0.5 g/kg [35, 49, 119], with an osmolarity of 286.4 mosm/L); group A10A Insulins and analogues – A10AAB01 #Insulin human regular [recombinant human DNA]** (0.1 IU/kg) [35, 49, 119]; group B05X Additives to intravenous solutions – B05XA05 #Magnesium sulfate** intravenously 30 mg/kg/hour (1 ml of solution contains 250 mg) [49]. Pathogenetic indications for their administration are described in section 1.2 of these clinical guidelines, subsection – Toxicodynamics. Mechanism of cardiotoxic action, and section 1.6 – Clinical picture of the disease or condition reflecting dyselectrolytemia. The volume and rate of drug administration are determined individually by a specialist depending on the need for rehydration, changes in the electrical conductivity of the heart against the background of solution administration, the patient's condition, and other parameters [88], with blood electrolyte monitoring [119].

Insulin human regular [recombinant human DNA]** and Magnesium sulfate** increase potassium influx into the cell, normalize its intracellular concentration, thereby eliminating hyperkalemia [49, 50]. Hyperkalemia exceeding 5.5 mEq/L, resistant to treatment with Insulin, can be considered prognostically unfavorable in cardiac glycoside intoxication [49, 88].

A similar effect – an increase in potassium influx into myocardial cells and reduction of hyperkalemia – is achieved by infusion of Sodium bicarbonate** [49, 50].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: the infusion dose or volume of the administered Sodium bicarbonate** solution given intravenously is determined depending on the venous and arterial blood levels of acid-base and water-electrolyte composition [82, 88, 89]. Sodium bicarbonate** increases potassium influx into the cell, thereby eliminating hyperkalemia [49]. Correction of acid-base balance disorders is of great importance in the course of the toxic process in acute poisoning by cardiac glycosides and drugs of similar action, since prolonged metabolic acidosis, which naturally develops in acute poisoning with hemodynamic impairment, can disrupt the function of various body systems [28, 49, 88].

Metabolic acidosis was defined as pH < 7.35 and bicarbonate (HCO₃^-) level < 22 mmol/L [90, 91]. Severe metabolic acidosis was defined as pH < 7.20 and HCO₃^-< 10 mmol/L, while moderate metabolic acidosis was defined as 7.20 ≤ pH < 7.30 and 10 ≤ HCO₃^-< 19 mmol/L [92].

In acute poisoning by cardiac glycosides and drugs of similar action, adults are administered Sodium bicarbonate**at a dose of 1–1.5 mEq/kg – 200–300 ml of a 4% solution; the further infusion dose is determined after monitoring the blood acid-base balance [35]. For children, depending on age and body weight, from 4 to 10 ml/kg (2–5 mEq/kg); the dose is administered over 4–8 hours [49].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: the drug #Magnesium sulfate** (1 ml contains 250 mg) is administered intravenously to adults at 2 grams (8 ml) over 20–30 minutes, and to children at 25–50 mg/kg, but not more than 2 grams [29, 35, 50, 88].

In case of hypomagnesemia, the drug is administered as a 25% solution intravenously to adults at a rate of 5–10 ml per hour [35]; to children at a rate of 30 mg/kg/hour [49]. Further dosing for adults and children is selected depending on the serum magnesium ion concentration and the clinical symptoms of the diagnosed disorder. Before administering the #Magnesium sulfate** solution in ampoules, it must be diluted with 0.9% Sodium chloride** or 5% Dextrose** injection solutions.

In case of moderate hypomagnesemia (without clinical symptoms), #Magnesium sulfate** is administered to adults intravenously at 6 grams (24 ml) diluted in 500 ml of 0.9% Sodium chloride** solution over 3 hours, followed by 5 grams (20 ml) diluted in 500 ml of 0.9% Sodium chloride** solution over the subsequent 6 hours [50, 88].

When correcting hypomagnesemia, it is necessary to clarify the genesis of this disorder (prolonged diuretic use) and its combination with hypokalemia (hypomagnesemia leads to persistent hypokalemia).

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: the drug #Magnesium sulfate** (1 ml – 250 mg) is administered to adults at 2–4 grams intravenously and to children at 25–50 mg/kg, but not more than 2 grams) [29, 50, 68, 93]. Further dosing of the drug for adults and children is selected depending on the serum magnesium ion concentration and the clinical symptoms of the diagnosed disorder.

The antiarrhythmic effect of the drug #Magnesium sulfate** [94, 95] is based on: preventing calcium ions from entering through the presynaptic membrane; disrupting the slow inward calcium current into cardiomyocytes. Its administration requires continuous ECG monitoring. Subsequent repeated administration of the drug #Magnesium sulfate** is determined by its serum concentration and the clinical effects of the drug, which are evaluated by the physician [88]. When serum magnesium rises above 2 mmol/L (4 mEq/L), deep tendon reflexes (knee-jerk reflex) diminish, which can be one of the diagnostic criteria for stopping its administration. Arterial hypotension may occur during the administration of #Magnesium sulfate**, which somewhat limits its use in acute poisoning. In the event of paroxysms of ventricular tachycardia accompanied by acute hemodynamic disturbances, emergency electrical cardioversion is required [67]. Once hypomagnesemia is confirmed in a patient, the specialist treating a patient with cardiac glycoside poisoning should consider both the indications of hypomagnesemia and the contraindications for its parenteral administration (severe hypotension and bradycardia; first- to third-degree atrioventricular block, chronic kidney disease, acute kidney injury) [29].

• Before correcting potassium balance, it is necessary to correct magnesium deficiency (or perform it in parallel) by intravenous administration of the drugs: #Magnesium sulfate**, #Potassium aspartate + Magnesium aspartate [49, 50].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: the medicinal product #Magnesium sulfate** (1 ml – 250 mg) is administered to adults at 2 grams (8 ml) intravenously over 20–30 minutes, and to children at 25–50 mg/kg, but not exceeding 2 grams) [29, 50, 68, 93]. Further dosing of the drug for adults and children is selected depending on the concentration of magnesium ions in blood serum and the clinical symptoms of the confirmed disorder.

In case of combined potassium and magnesium deficiency, drugs are administered intravenously diluted in a 5% #Dextrose** solution: #Potassium aspartate + Magnesium aspartate for adults 20 ml [35], for children 10–20 ml [49, 64]; #Potassium aspartate + Magnesium aspartate for adults at a rate of 10 ml/hour [35, 49]. The administered doses of medicinal products require monitoring of plasma potassium [35].

• All patients with confirmed hypokalemia against the background of acute poisoning with cardiac glycosides and drugs of similar action must undergo correction via intravenous administration of the drug Potassium chloride** [35, 49, 50].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: as a rule, hypokalemia in cardiac glycoside poisoning most often occurs against the background of long-term diuretic use [49]. When the serum potassium level drops below 3.5 mEq/L, its deficit is 200 mEq and requires replacement [50]. Hypokalemia is eliminated by intravenous administration of 0.5% Potassium chloride** solution, which is administered at a rate of 1.5–2.5 mEq/min in a 10% #Dextrose** solution in both adults [35] and children [49].

3.3.2. Correction of bradyarrhythmia and conduction disorders

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: the dose of the drug Dopamine** should be selected individually for adults – 0.5–1.5–3.5–4–10–20 mcg/kg/min, starting from 0.5 mcg/kg/min up to 5 mcg/kg/min (the dose stimulating dopaminergic receptors), from 5 mcg/kg/min to 15 mcg/kg/min (the dose stimulating adrenergic receptors), from 15 mcg/kg/min to 25 mcg/kg/min (the dose exerting predominantly noradrenergic action) [35]; children are administered intravenously at a rate of 4–6 mcg/kg/min, maximum 10 mcg/kg/min [35, 49, 64]; C01CA07 Dobutamine** is administered intravenously to adults at a dose of 2.5–10 mcg/kg/min [50, 65], in individual cases the dosage may be up to 40 mcg/kg/min. It is administered to children with dose titration depending on clinical data at a dose of 1–15 mcg per 1 kg of body weight per min [64, 119].

A dose of 0.5–3 mcg/kg/min predominantly acts on dopamine receptors, causing dilation of renal, mesenteric, and cerebral blood vessels; a dose of 2–10 mcg/kg/min stimulates postsynaptic β₁-adrenoceptors, which causes a positive inotropic effect and an increase in cardiac output – systolic blood pressure and pulse pressure increase; a dose of 10 mcg/kg/min and higher leads to stimulation of α₁-adrenoceptors, which is accompanied by an increase in total peripheral vascular resistance (TPVR) and heart rate; the increase in cardiac output and TPVR leads to an increase in systolic and diastolic blood pressure [35].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: treatment of bradycardia associated with complete bundle branch block begins with pharmacotherapy. The drug #Atropine** is most effective in complete bundle branch block at the His-Purkinje level and in bradycardias. Due to the short duration of action, the drug #Atropine** is usually used as an "initial" drug before longer-term therapy, such as the use of a beta-adrenergic drug or transesophageal pacing [29, 35, 49].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

3.3.3. Correction of atrial fibrillation

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: evaluate bleeding risk in all patients prior to prescribing antithrombotic therapy, identifying non-modifiable and modifiable risk factors for bleeding [66]; to assess the risk of thromboembolic complications (ischemic stroke, transient ischemic attacks, and systemic thromboembolism), all adult patients must undergo stroke and systemic thromboembolism prophylaxis upon confirmation of nonvalvular atrial fibrillation using the CHA₂DS₂-VASc score [66]; in patients with confirmed atrial flutter undergoing rhythm restoration when planning cardioversion, anticoagulant therapy should be administered following the same regimen as in patients with AF [66]; adult patients with atrial fibrillation and atrial flutter should adhere to the antiarrhythmic pharmacotherapy strategy outlined in the relevant clinical guidelines: Atrial fibrillation and atrial flutter in adults ID382_1 [69]; management of atrial fibrillation in children should be performed taking into account the stages of antiarrhythmic therapy delivery [97]; the pathophysiological mechanism underlying altered electrical processes that manifest as atrial fibrillation is exogenous intoxication with cardiac glycosides and drugs of similar action [28, 49, 97].

3.3.4. Correction of ventricular tachycardia (tachyarrhythmia) and ventricular fibrillation

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: #Lidocaine**, a drug from the group "Class I and III Antiarrhythmic Drugs" – Class Ib antiarrhythmic drug [4], should be used in adults at a bolus dose of 1-2 mg/kg body weight. Maintenance therapy is 1-4 mg per minute in saline (or 20-50 mcg/kg/min.) [35, 67]; for children, it is administered as a bolus of 1 mg/kg followed by 0.5-0.75 mg/kg every 5 minutes until the desired pharmacotherapeutic effect is achieved [49]. The total dose should be up to 5 mg/kg [49]. After administering the specified bolus dose, if there is a positive effect, the drug can be prescribed in maintenance doses of up to 15 mcg/kg/min. [49]. Lidocaine** is the only drug mandated for VT development due to cardiac glycoside intoxication. Unlike other drugs used to terminate paroxysms of ventricular tachycardia, Lidocaine** in the specified doses does not significantly affect the analyzed ECG intervals (only shortening of QTc may be observed). Administration of #Lidocaine** may be accompanied by its own toxic effects – CNS depression, convulsive seizure, prolongation of the P-R interval and QRS complex, and shortening of Q-T [49].

The algorithm for terminating VT paroxysms is presented in the Clinical Guidelines «Ventricular rhythm disorders. Ventricular tachycardias and sudden cardiac death» (ID 569), Table A3.2 «Drugs for terminating VT paroxysms in adults» [67].

In atrial fibrillation, Lidocaine** is ineffective [50].

3.3.5. Antidote therapy

The primary cardiotoxic effect or selective myocardial toxicity in acute poisonings with cardiac glycosides and similar agents manifests as the toxicants' effect on the chrono-, dromo-, and inotropic functions of the heart (suppression of automaticity – sinus bradiarrhythmia, atrial and ventricular extrasystole, atrial and ventricular (non-sinus) tachyarrhythmia, ventricular fibrillation, asystole; conduction block – I-II-III degree AV block, complete AV block; reduction of contractile function – hypoxemia, impaired cell membrane permeability to electrolytes, hypoxia) and vascular tone – hypotension. Hypokalemia enhances the toxic pharmacological effects of cardiac glycosides. Hyperkalemia contributes to the occurrence of rhythm disorders, conduction blocks, and asystole.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: drug of the pharmacological group V03AB Antidotes – Sodium dimercaptopropanesulfonate** (5% solution for intramuscular and subcutaneous administration, 1 ml of the drug contains 50 mg of the drug). The drug is administered in the first two days of digitalis intoxication intramuscularly to adults at a single dose of 250-500 mg (5-10 ml of 5% solution) 3-4 times a day, subsequent administration 1-2 times a day until the cardiotoxic effect ceases [100]; to children, 1 ml of 5% solution per 10 kg of weight intramuscularly in the toxicogenic period until the cardiotoxic effect is terminated (in the first 2 days – 3 times a day, subsequent days 1-2 times a day) [49].

Level of Evidence (LE) – 5, Grade of Recommendation (GR) – C.

Comments: drug of the pharmacological group H02 Systemic corticosteroids H02AB06 #Prednisolone** (30 mg/ml solution) is administered intravenously at a dose of 90 mg [35], in shock states in adults intravenously or intramuscularly 90-120 mg, daily dose 300-390 mg; for children aged 2 to 12 months, it is administered at 2-3 mg/kg, from 1 to 14 years – 1-2 mg/kg, if necessary, repeated administration at the specified doses after 30 minutes [64].

When choosing a drug for cardiomyocyte membrane stabilization and reduction of cardiotoxicity, the physician must evaluate the indications and contraindications specified in the instructions for medical use of the drugs (section "Interaction with other medicinal products").

3.3.6. Refrain from use

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: in case of hyperkalemia of a different etiology, calcium administration has a good clinical effect, however, in case of cardiac glycoside poisoning, the use of calcium salts is dangerous because patients already have an elevated intracellular concentration [29] and its administration can lead to toxic effects and ventricular fibrillation [49].

3.3.7. Detoxification

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: gastric lavage is performed at any time of toxicant exposure (enterohepatic circulation of digoxin and digitoxin) [35, 49];

gastric lavage is performed in the absence of life-threatening cardiac rhythm disorders in the patient, as this medical procedure can cause a vagal effect – provoke bradycardia, ventricular fibrillation, and asystole (especially in children) [25, 26, 64, 119].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: gastrointestinal sorption is based on the properties of intestinal adsorbents intended for enteral administration to bind toxic substances. The medical technique is based on oral or tube administration of intestinal adsorbents into the stomach or intestine (after intestinal intubation).

The medicinal product A07BA01 #Activated charcoal is used for gastrointestinal sorption in the form of a tablet suspension at 0.5–1 g per 1 kg of body weight for adults [25, 26, 29, 35, 101]. For children, it is administered at 1 g per kg of body weight up to 5 years of age (weight up to 20 kg) and 0.5–1 g per 1 kg of body weight for children over 5 years of age (weight over 20 kg) in two to three divided doses [28]. Subsequent administration (for maximum enterosorption effect) in children is carried out at a rate of 1-2 g per hour or at intervals of 2–6 hours (0.25–0.5 g per kilogram of body weight) [29, 49, 64, 119]. The duration of use of Activated charcoal (and other A07B Intestinal adsorbents; A07BC Other intestinal adsorbents) is determined individually and depends on the dynamics of clinical manifestations.

The medicinal product Polymethylsiloxane polyhydrate (hydrogel, paste) with a porous structure possesses a selective sorption action via the mechanism of molecular adsorption toward medium-molecular toxic metabolites and absorbs high-molecular toxins through a gel-precipitation mechanism. It is used as a medicinal product—an enterosorbent—applied to bind and eliminate toxic substances from the gastrointestinal tract. Polymethylsiloxane polyhydrate is not absorbed in the gastrointestinal tract. Adults are prescribed 15 g to 22.5 g (1–1.5 tablespoons) 3 times a day. The daily dose is 45–67.5 grams. Children aged 5 to 14 years are prescribed 10 g (1 dessert spoon) 3 times a day. The daily dose is 30 grams. For children from 14 years of age, the dose of the medicinal product is similar to that for adults. Children under 5 years of age are prescribed 5 g (1 teaspoon) 3 times a day. The daily dose is 15 g (up to 22.5 g). The duration of treatment for acute poisonings is 3 to 5 days [25, 26].

The medicinal product of the A07BC group, Hydrolyzed lignin, is a natural enterosorbent consisting of wood component hydrolysis products, which possesses a nonspecific detoxifying effect [102, 103] and is used in adults and children upon exposure to toxicants [11, 106]. For enterosorption and interruption of the enterohepatic circulation of toxins, the contents of a package of Hydrolyzed lignin are diluted in 50–100 ml of water and taken orally or administered via a tube. The average dose for children is 0.5–1 g per 1 kg of body weight; for children over 7 years of age, the dose is the same as for adults [28]; for adults, a dose of 0.5–1 g per kg of body weight is used [35, 106] in 3–4 divided doses.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: intestinal lavage allows the removal of unabsorbed toxicants entering the intestine [100, 101].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: forced diuresis is a detoxification method based on the use of medicinal products that promote an increase in diuresis, and is carried out in three stages—hypovolemia is preliminarily compensated by intravenous administration of infusion solutions of groups B05BB01 – Electrolytes; B05BB02 – Electrolytes in combination with carbohydrates, followed by the administration of the medicinal product #Furosemide** C03CA01 at a dose of 100–150 mg for adults [106], 1–3 mg/kg intravenously for children [100, 119], and subsequent administration of solutions of groups B05BB01 – Electrolytes; B05BB02 – Electrolytes in combination with carbohydrates [106].

Forced diuresis does not accelerate the elimination of digoxin due to its large volume of distribution (4–10 L/kg) [29]. Forced diuresis has low efficacy in cardiac glycoside (CG) poisoning [49].

When using this method, the volume of distribution of the toxic substance must be taken into account [29]. The use of forced diuresis helps reduce hyperkalemia [49].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: dialysis-filtration detoxification methods do not accelerate the elimination of digoxin** due to its large volume of distribution [29, 35]. In poisoning with the drug Digoxin** with an exposure of more than 4–6 hours, only 1% of the toxicant is in the plasma and about 25% is bound to plasma proteins [35]. Hemodialysis corrects hyperkalemia arising from cardiac glycoside poisoning [35].

3.3.8. Treatment of gastrointestinal and other organ dysfunctions

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: to reduce the clinical manifestations of acute toxic gastroenteritis (symptoms of nausea and vomiting) and accelerate the passage of stomach and intestinal contents during enterosorption, parenteral administration of a medicinal product from group A03F Gastrointestinal motility stimulants, A03FA01 #Metoclopramide** is required: intravenous administration of 10–20 mg for adults, 0.1 mg/kg for children [35, 49, 119].

3.3.9. Treatment of respiratory disorders

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: the main goal of respiratory support in ventilatory failure is the replacement of lost or sharply weakened spontaneous breathing due to impaired function of the respiratory center against the background of pronounced hypotension or other pathological conditions leading to the depression or weakening of the sensitivity of central chemoreceptors, which causes hypoventilation accompanied by hypercapnia and hypoxemia [28, 35, 70, 82, 84, 100].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

3.3.10. Correction of homeostasis disorders

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comment: the most clinically significant (considering the pathogenesis of poisoning) medicinal product is #Meglumine sodium succinate** (1.5%), administered as an intravenous drip of 400–800 ml twice a day for adults; children over one year of age are administered 200 ml as an intravenous drip twice daily [35].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comment: considering the presented clinical goal, the most pharmacologically justified drug is C03CA01 – #Furosemide** administered intravenously and intramuscularly. The rate of intravenous administration should not exceed 4 mg per minute. In patients with severe renal impairment (with serum creatinine concentration > 5 mg/dL), intravenous administration of the drug is used at a rate not exceeding 25 mg per minute. 0.9% sodium chloride solution** can be used for dilution. The diluted solution of the drug should be used immediately. The recommended dose for adults for the correction of hyperkalemia – 40–80 mg intravenously after infusion therapy [35]; for a diuretic effect, a single dose is 100–150 mg [100, 106]; in children – 1–3 mg/kg (intramuscularly, intravenously) [100, 119].

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Comments: the drug is administered as an intravenous infusion of 10 ml twice a day, diluted in 100–200 ml of 20% Dextrose**, as an option for neurometabolic therapy [109], with an interval of 8–12 hours for 5 days; 20 ml as an infusion in 200 ml of a 5% or 10% Dextrose** solution in acute poisonings accompanied by toxic and hypoxic encephalopathy, coma [35, 110]. Administration rate is 3–4 ml/min.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Rehabilitation is aimed at restoring somatovegetative and mental functions impaired as a result of acute chemical intoxication. In an uncomplicated course of acute poisoning, rehabilitation is not required.

There are no special recommendations for the rehabilitation of patients during the somatogenic stage of acute poisoning complicated by the development of cardiomyopathy. Patients undergo rehabilitation measures just like patients with other cardiovascular pathologies [126].

5. Prevention and Dispensary Observation

Level of Reliability of Evidence (LRE) – 5, Level of Recommendation Validity (LRV) – C.

6. Organization of Medical Care

Medical care for patients with acute poisonings with cardiac glycosides is provided in accordance with the Order of the Russian Ministry of Health No. 925n dated November 15, 2012, "On approval of the Procedure for providing medical care to patients with acute chemical poisonings" [116].

Hospitalization of patients with acute poisoning with cardiac glycosides and drugs of similar action is carried out in the toxicology department (centers for the treatment of acute poisonings, specialized departments of a medical organization in the absence of centers). Hospitalization for emergency indications is carried out in the intensive care unit.

The duration of hospitalization is determined by the severity of the poisoning.

According to this order, medical care for patients with acute poisoning is provided in the following forms:

- primary health care;

- emergency medical care, including specialized emergency medical care;

- specialized medical care.

Medical care is provided under the following conditions:

- outside a medical organization (at the location of the ambulance team dispatch, as well as in a vehicle during medical evacuation);

- out-patient (in conditions not providing for round-the-clock medical monitoring and treatment), including at home upon calling a medical worker;

- on an inpatient basis (under conditions providing for round-the-clock medical observation and treatment).

Medical care is provided in the following forms:

- emergency – for acute chemical poisonings that pose a threat to the life of a patient with acute chemical poisonings;

- urgent – for acute chemical poisonings without obvious signs of a threat to the life of a patient with acute chemical poisonings.

Primary health care includes: primary pre-medical health care; primary medical (physician-led) health care; primary specialized health care. Primary pre-medical health care is provided by mid-level medical personnel. Primary medical health care is provided by a general practitioner, district general practitioner, or family physician. Primary specialized health care is provided by medical specialists.

Ambulance, including specialized ambulance, medical care is provided by paramedic dispatch teams and physician-led dispatch teams. Ambulance, including specialized ambulance, care is provided in emergency and urgent forms outside a medical organization as well as in inpatient settings of a medical organization. When providing ambulance care, medical evacuation is carried out when necessary, which includes air-medical and standard medical evacuation.

Specialized, including high-tech, medical care includes diagnosis, treatment of acute chemical poisoning, other diseases and conditions requiring special methods and complex medical technologies, measures aimed at preventing complications caused by acute chemical poisoning, as well as medical rehabilitation.

Medical care for patients with acute chemical poisoning is provided:

- in centers (departments) of acute poisonings;

- in medical organizations that include an intensive care unit (ward, block).

In the absence of a center (department) of acute poisonings in a medical organization and one that includes an intensive care unit (ward, block), the provision of medical care to patients with severe acute chemical poisonings is carried out in the intensive care unit (ward, block), and for patients with moderate acute chemical poisonings and for patients transferred from the intensive care unit (ward, block) – in the therapeutic departments of the medical organization.

If the medical organizations providing care lack specialized toxicological units, round-the-clock informational and consultative support is provided by the information and consultation toxicological center (department) via telephone.

The provision of medical care to patients with acute chemical poisonings under the age of 15 is carried out in a center (department) of acute poisonings or an intensive care unit (ward, block) featuring an acute poisoning ward operating as part of a medical organization providing medical care to children, or on specially allocated pediatric beds in the center (department) of acute poisonings of a medical organization providing medical care to the adult population.

If medical care requires the mandatory use of extracorporeal detoxification methods (hemodialysis, hemoperfusion, etc.) as decided by a medical board involving a toxicologist from the acute poisoning center (department) and in the absence of medical contraindications for transportation, patients with acute chemical poisoning are transferred to the acute poisoning center (department) of a medical organization.

In the event of complications requiring specialized treatment (post-hypoxic encephalopathy resulting in a vegetative state, exacerbation of a mental illness, etc.), patients are subject to transfer to the appropriate department of the medical organization according to the disease (complication) profile.

6.1. Indications for hospitalization

All injured patients with acute poisoning with cardiac glycosides and drugs of similar action should preferably be hospitalized in a specialized center for acute poisonings. In the absence of a center for acute poisonings, patients with severe poisoning and complications, especially with impaired vital functions, should preferably be hospitalized in an intensive care unit or an intensive care ward of the emergency department where hemodialysis is available, followed by hospitalization in a center for acute poisonings or, upon condition stabilization, subsequent transfer to a specialized department.

The duration of hospitalization is determined by the severity of the poisoning.

6.2. Indications for patient discharge from the hospital

Treatment in the intensive care unit is carried out until vital function impairments stabilize and detoxification measures are completed, followed by rehabilitation measures in the acute poison treatment center, therapeutic, and pediatric departments.

Duration of hospitalization is determined by the severity of acute poisoning with cardiac glycosides and drugs of similar action.

Average duration of inpatient treatment:

1. mild severity – from 3 to 7 bed-days;

2. - moderate severity – from 10 to 14 bed-days;

3. - severe without complications – from 21 to 28 bed-days;

4. - severe with complications (cardiomyopathy, central nervous system disorders) – from 30 to 60 bed-days.

In case of "group" diseases – acute poisonings with cardiac glycosides and drugs of similar action, develop a unified strategy for providing care – choose the direction of medical evacuation of patients, and whenever possible, evacuate to a medical organization that includes a specialized department for providing medical care to patients [85].

The choice of the direction of medical evacuation will optimize the treatment strategy in providing care and provide timely and effective assistance to the victims [85].

In the event of an unfavorable outcome (death of the patient), a forensic medical examination and a set of forensic autopsy studies must be performed in accordance with the Order of the Russian Ministry of Health No. 491n dated September 25, 2023, "On approval of the procedure for conducting a forensic medical examination" (forensic medical diagnosis in patients with acute poisoning with cardiac glycosides and drugs of similar action should be based on a set of forensic autopsy studies and the interpretation of forensic autopsy data) [121, 122, 123].

The resulting failure of body systems leads to an unfavorable outcome and the performance of a forensic medical examination and a set of forensic autopsy studies, the conclusion on which is drawn by a forensic medical expert [86, 121, 122, 123].

7. Additional Information

Factors influencing the course and outcome of the disease.

1. Advanced and senile age of the patient;

2. Presence of chronic cardiovascular, hepatic, or renal diseases, as well as metabolic disorders.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Yatsinyuk, Boris Borisovich – Chief Toxicologist of the Department of Health of the Khanty-Mansi Autonomous Okrug – Yugra, Candidate of Medical Sciences, Associate Professor, Anesthesiologist-Resuscitator, Toxicologist of the Intensive Care Units at the budgetary institution of KhMAO-Yugra "Khanty-Mansiysk Clinical Psychoneurological Hospital"; Associate Professor, Department of General Surgery and Anesthesiology, Medical Institute, Orel State University named after I.S. Turgenev.

2. Lodyagin, Alexey Nikolaevich – Doctor of Medical Sciences, Chief Freelance Specialist Toxicologist of the Ministry of Health of the Russian Federation, Head of the Department of Clinical Toxicology, St. Petersburg Research Institute of Emergency Care named after I.I. Dzhanelidze.

3. Batotsyrenov Bair Vasilyevich – Doctor of Medical Sciences, Chief Researcher at the Department of Clinical Toxicology, Dzhanelidze St. Petersburg Research Institute of Emergency Medicine.

4. Alyanov, Alexander Leonidovich – Member of the Government of the Orel Region, Head of the Department of Health of the Orel Region, Candidate of Medical Sciences, Associate Professor.

5. Lukin, Vadim Anatolyevich – Doctor of Medical Sciences, Senior Researcher at the Department of Clinical Toxicology, St. Petersburg Research Institute of Emergency Care named after I.I. Dzhanelidze.

6. Irina A. Shikalova – Ph.D. in Medicine, Senior Researcher at the Department of Clinical Toxicology, Saint Petersburg Research Institute of Emergency Medicine named after I.I. Dzhanelidze.

7. Narziculov Rustam Abdukhalimovich – Doctor of Medical Sciences, Researcher at the Department of Clinical Toxicology, St. Petersburg Research Institute of Emergency Care named after I.I. Janelidze.

8. Oleg A. Kuznetsov – Candidate of Medical Sciences, Researcher at the Department of Clinical Toxicology, Saint Petersburg Research Institute of Emergency Medicine named after I.I. Джанелидзе.

9. Gavrikov, Pavel Pavlovich – Forensic Medical Expert, budgetary institution of KhMAO-Yugra "Bureau of Forensic Medical Expertise".

10. Zhidkov Vyacheslav Alexandrovich – Head of the Intensive Care Units at the Khanty-Mansiysk Clinical Psychoneurological Hospital.

11. Kosarev Alexey Nikolaevich – Candidate of Medical Sciences, Anesthesiologist-Resuscitator at the Intensive Care Units, Khanty-Mansiysk Clinical Psychoneurological Hospital (Budgetary Institution of Khanty-Mansi Autonomous Okrug – Ugra).

12. Barats Ekaterina Alekseevna – Anesthesiologist-Resuscitator at the Intensive Care Units, Khanty-Mansiysk Clinical Psychoneurological Hospital (Budgetary Institution of Khanty-Mansi Autonomous Okrug – Ugra).

13. Leonova, Elena Vladimirovna – Anesthesiologist-Resuscitator of the Intensive Care Units at the budgetary institution of KhMAO-Yugra "Khanty-Mansiysk Clinical Psychoneurological Hospital".

There is no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of these clinical guidelines:

1. anesthesiologist-intensivist;

2. gastroenterologist;

3. infectious disease physician;

4. allergist-immunologist;

5. cardiologist;

6. clinical laboratory diagnostics physician;

7. neurologist;

8. neurosurgeon;

9. general practitioner (family physician);

10. otorhinolaryngologist;

11. emergency physician;

12. forensic medical expert;

13. internist;

14. district general practitioner;

15. toxicologist;

16. transfusiologist;

17. functional diagnostics physician;

18. surgeon;

19. endoscopist;

20. psychiatrist-narcologist.

Methodology for Developing Clinical Guidelines

Working group members independently performed a systematic search and selection of publications. The search was conducted in the PubMed search engine (http://www.ncbi.nlm.nih.gov/pubmed/), the Cochrane Library (http://www.cochranelibrary.com/), the scientific electronic library eLIBRARY.ru (http://elibrary.ru/defaultx.asp), as well as clinical trial registries: https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ctrsearch/search. A total of 220 publications were found, and 101 publications were selected. Based on the selected publications, thesis-recommendations were formulated, which were evaluated using the scales for assessing the levels of evidence certainty and diagnostic methods, scales for assessing the levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, rehabilitation interventions), and scales for assessing the grades of recommendation (GOR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions) (Table 2, Table 3, Table 4). Subsequently, each thesis-recommendation was thoroughly discussed at the general meeting of the working group, and consensus was reached in all cases of disagreement.

Table 7 – Scale for assessing the levels of evidence certainty (LEC) for diagnostic methods (diagnostic interventions)

Table 8 – Scale for assessing the levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)

Table 9 – Scale for assessing the grades of recommendation (GOR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)

Procedure for updating clinical guidelines.

The clinical guideline update mechanism provides for their systematic updating at least once every three years, as well as when new evidence-based medicine data appear regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or when justified additions/comments to previously approved clinical guidelines arise, but not more frequently than once every 6 months.

Appendix A3. Reference Materials

1. Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Healthcare Protection in the Russian Federation".

2. Order of the Russian Ministry of Health No. 203n dated May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care."

3. Order of the Ministry of Health and Social Development of the Russian Federation No. 40 dated January 27, 2006, "On the organization of chemical and toxicological studies in the analytical diagnosis of the presence of alcohol, narcotic drugs, psychotropic and other toxic substances in the human body."

4. Order of the Russian Ministry of Health No. 925n dated November 15, 2012, "On approval of the Procedure for providing medical care to patients with acute chemical poisoning."

5. Order of the Russian Ministry of Health No. 804n dated October 13, 2017, "On approval of the nomenclature of medical services."

6. Federal Law No. 489-FZ dated December 25, 2018, "On amendments to Article 40 of the Federal Law 'On compulsory health insurance in the Russian Federation' and the Federal Law 'On the basics of protecting the health of citizens in the Russian Federation' regarding clinical guidelines."

7. Order of the Russian Ministry of Health No. 103n dated February 28, 2019, "On approval of the procedure and timelines for the development of clinical guidelines, their revision, the standard form of clinical guidelines and requirements for their structure, composition, and the scientific validity of the information included in clinical guidelines."

8. Order of the Russian Ministry of Health No. 919n dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to the Adult Population in the Profile 'Anesthesiology and Critical Care Medicine.'"

9. Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019, "On approval of the list of vital and essential drugs, as well as lists of medicinal products for medical use, including medicinal products for medical use and the minimum assortment of medicinal products necessary for the provision of medical care."

10. Order of the Russian Ministry of Health No. 491n dated September 25, 2023, "On approval of the Procedure for conducting forensic medical examinations."

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Information for a patient admitted with impaired consciousness (obtundation, stupor, coma; impaired mental functions – delirium, hallucinations, and other forms of impairment) is provided after the recovery of consciousness and mental functions, and must contain information on complications that occurred in the toxicogenic stage of poisoning, and planned treatment during the rehabilitation process (if required for the given patient).

In mild and moderate acute poisonings with cardiac glycosides and drugs of similar action, the patient is informed about the health hazards of these toxic substances, potential complications, long-term consequences of the poisoning, planned examinations (chemical-toxicological, clinical-biochemical, instrumental), and treatment (detoxification methods, pathogenetic and specific therapy). The patient (or their legal representatives) signs an informed voluntary consent for the proposed scope of examination and treatment.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Glasgow Coma Scale

Russian name: Glasgow Coma Scale, GCS.

Original name (if available): The Glasgow Coma Scale, GCS.

Source (official developer website, validation publication): Teasdale G., Jennett B. Assessment of coma and impaired consciousness. A practical scale. // The Lancet. – 1974. – Vol. 2, № 7872. – P. 81-84.

Type: rating scale.

Purpose: for quantitative assessment of the severity of coma and neuropsychiatric disorders.

Content:

Key (interpretation of obtained results):

15 points – clear consciousness

10–14 points – moderate and deep obtundation

8–10 points – stupor

6–7 points – moderate coma

4–5 points – terminal coma

3 points – brain death

Appendix G2. Poisoning Severity Score

Name in Russian: Poisoning severity score.

Original name: Poisoning severity score (The European Association of Clinical Poison Centers and Clinical Toxicologists).

Source: Persson H.E. et al. Poisoning severity score. Grading of acute poisoning. Assessment of coma and impaired consciousness. A practical scale. // J. Clin. Toxicol. – 1998. – Vol. 36, № 3. – P. 205-213.

Type: rating scale.

Purpose: for quantitative assessment of the severity of acute poisoning.

Content: