Intensive Care of Acute Poisoning - A. V. Hovenko 2010

Main types of acute poisoning and their treatment
Plant poisoning
Mushroom poisoning

Poisoning can be caused by about 20 species of mushrooms. Depending on The Nature of the toxic substances contained in the mushrooms, poisonings can be conditionally divided into three main types:

1) the first category includes mushroom poisonings caused by species containing helvellic acid (true and false morels);

2) the second category involves poisonings by mushrooms containing phalloidin, phalloin, and amanitin (death cap and closely related species);

3) the third category comprises poisonings by mushrooms that release muscarine and atropine-like Alkaloids (fly agaric, panther cap, porphyry mushroom, and other Amanita species).

Depending on the time interval between mushroom ingestion and the onset of the first clinical symptoms, toxic mushrooms are divided into two groups. The first group includes poisonous mushrooms that trigger gastroenteritis syndrome within the first 6 hours: morels, false morels, destroying angel, Satan's bolete, and others. In addition to gastroenteritis, they can induce other clinical syndromes:

1) muscarine-like syndrome (perspiration, salivation, colic, pulmonary edema);

2) anticholinergic syndrome (drowsiness, delirium, hallucinations);

3) hallucinogenic syndrome caused by psilocybin and its analogs;

4) antabuse-like reaction syndrome, observed when consuming this group of mushrooms in combination with alcohol.

The second major group of mushrooms, ingestion of which results in mortality rates of 50–95% (Cherny V.I., Kuznetsova I.V., Tyumentsev S.G. et al., 2003), consists of species that cause primary clinical symptoms 6 or more hours after consumption. The most prominent representatives of this group are poisonous mushrooms of the genus Amanita and several others, including:

1) Amanita verna (destroying angel) – the "Angel of Death" – contains alpha- and beta-amanitin, phalloidin, and phalloin toxins;

2) Amanita virosa (European destroying angel) – contains amanitins and virosin toxins;

3) Amanita phalloides (death cap) – known as the "Death's HEAD" or "Death Cup";

4) Amanita verna (pointed or conical death cap);

5) Lepiota helveola (meat-red dapperling) – contains phallotoxin and amanitin;

6) Galerina marginata (bordered galerina) – contains phallotoxins and amatoxins.

Death cap poisoning. The death cap (white, yellow, and green varieties) and closely related mushroom species contain the following types of toxins:

1) thermolabile toxins – substances that decompose at temperatures of 70 °C, such as phallin and amanitohaemolysin;

2) thermostable toxins – toxins that are resistant to thermal Processing and drying:

a) fast-acting toxins – substances whose effects manifest within 6–12 hours (phallotoxins: phalloin, phalloidin);

b) slow-acting toxins – substances whose effects manifest within 28–46 hours (amanitotoxins: a-, ß-, and γ-amanitins, amanin).

It should be noted that amanitotoxins are 20 times more toxic than phallotoxins. The lethal dose of ß-amanitin is 0,1 mg/kg. The mortality rate for death cap poisoning is 60–70%, and reaches 90% in children.

The Pathogenesis of this poisoning is driven by the specific tropism of death cap toxins for hepatocytes.

Phalloidin interacts with The Cell membrane, disrupting it and penetrating the interior of the hepatocyte, which leads to calcium release and a corresponding increase in intracellular potassium levels. From this point, damage to the Lysosomes and The Endoplasmic reticulum of the hepatocyte occurs. Phalloidin binds to F-Actin and rigidly blocks The Structure of aggregated DNA filaments. Compared to amanitin, phalloidin acts quite rapidly. It possesses high absorptive capacity and, upon entering the gastrointestinal tract, destroys mucosal Cells. This results in severe, intractable vomiting, diarrhea, and Hemorrhage.

Following absorption, amanitin enters the Liver, which becomes the primary organ affected. Because amanitins are excreted via the urine, the Kidneys are the final Organs to sustain damage from these toxins.

Amanitin interacts with RNA polymerase I, which copies heterogeneous nuclear RNA, a precursor to tRNA. This, in turn, leads to cellular necrosis and the cessation of Protein Synthesis. Cellular steatosis develops, subsequently causing cell death. A single amanitin molecule binds to one polymerase molecule with a Molecular Weight of approximately 500 Daltons. This binding is irreversible.

Amanitins block the polymerase, causing the cell to perish not As a result of a direct toxic impact, but due to the blockade of vital cellular Functions.

The course of poisoning by the death cap (*Amanita phalloides*) consists of four phases:

Phase I (latent, asymptomatic). Lasts 8–48 hours, occasionally 5–12 hours. It is associated with the mucosal damage of The Stomach caused by toxins. It develops slowly, without overt clinical symptoms.

Phase II (gastrointestinal). Lasts 12–24 hours and is characterized by cholera-like diarrhea, sometimes accompanied by hemorrhage, severe fluid loss, vomiting, hypokalemia, hyponatremia, hypotension, acidosis, a rapid drop in hematocrit, hypoglycemia, and leukocytosis.

Phase III (secondary latent). Lasts approximately 12–24 hours. It is characterized by clinical improvement in the patient's condition, yet is accompanied by elevated transaminase levels.

Phase IV (hepatorenal) begins 36 hours after mushroom ingestion, but reaches its peak between the 3rd and 5th days. Due to impaired cellular PROTEIN SYNTHESIS AND cell death, acute Liver failure develops. Transaminase levels rise sharply, the liver enlarges, and jaundice, anorexia, encephalopathy, hypoglycemia, hyperphosphatemia, and oliguria appear.

Gastroenteritic syndrome in death cap poisoning develops more than 6 hours after mushroom consumption. By the end of the first 24 hours, the initial signs of hepatic dysfunction may appear, subsequently leading to fulminant liver failure, sometimes accompanied by damage to other organs and systems, up to and including renal failure.

However, quite frequently on the 2nd or even the 3rd day, these poisonings present no pronounced clinical symptoms. Such a period of "false well-being" is often the cause of fatal errors, as it prompts patients to forgo seeking medical attention and prevents medical staff from implementing a full regimen of intensive and extracorporeal detoxification therapy.

Differential Diagnosis

1. It is essential to differentiate between the period of "false well-being" in patients who have ingested mushrooms containing amanitins, phalloidins, and other potentially lethal poisons, and a genuine recovery in patients who have consumed improperly prepared mushrooms or those containing other, less toxic substances, where the condition resolves entirely as gastroenteritis without vital organ damage.

2. It is practically impossible to avoid a fatal outcome in cases where specialized care based on intensive and extracorporeal therapy is initiated later than the third day post-poisoning.

3. The range of extracorporeal therapy Methods, their sequence, and intensity should be based not only on the clinical picture, but also on the results of specific Laboratory tests (determining the activity levels of Enzymes such as Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT)).

4. The methods of intensive and extracorporeal therapy must be readily accessible, and laboratory tests sufficiently inexpensive and rapid to perform.

Violating these principles leads to a sharp increase in mortality rates, despite the administration of intensive care measures, which in such instances will amount to a "desperate intervention."

Thus, baseline intensive care must include the following actions:

1. Mandatory gastric and intestinal lavage, along with the administration of enterosorbents, regardless of the time elapsed or the Clinical presentation of the poisoning.

2. Carefully regulated Infusion and transfusion therapy, since dehydration and electrolyte imbalances—primarily caused by severe gastroenteritis—are formidable complications in their own right and require precise correction.

In addition to comprehensive drug therapy, various stages of mushroom poisoning Treatment utilize hemocarbon perfusion, high-volume plasmapheresis (including plasma filtration), hemofiltration, hemodiafiltration, and albumin dialysis.

Toadstool poisoning. The fly agaric (*Amanita muscaria*) contains the alkaloids muscarine and muscaridine, which exert a neurotoxic effect associated with the excitation of M-cholinergic receptor systems. It also contains bufotenine, muscazone, and Other Compounds with hallucinogenic properties.

Symptoms of fly agaric poisoning manifest within 30–40 minutes (occasionally up to 2 hours). Patients experience nausea, vomiting, abdominal pain, excessive salivation and sweating, and dyspnea. A characteristic symptom is miosis (constriction of the pupils). Further progression of the poisoning leads to diarrhea (watery stools), general weakness, a drop in Blood pressure, and Cardiac Arrhythmias. Neuropsychiatric disorders may also occur: confusion, hallucinations, delirium, and convulsions. The pupils are constricted, Vision is impaired, and the pupillary light reflex may be absent. Respiration becomes wheezing, with moist rales auscultated upon examination.

Treatment. 1. Gastric lavage, administration of saline laxatives (20–30 g of magnesium or sodium sulfate).

2. Administration of atropine sulfate as an antidote—subcutaneous injections of 1 ml of a 0.1% solution should be repeated 3–4 times at intervals of 30–40 minutes (until symptoms of poisoning subside). In severe cases of poisoning, atropine sulfate is administered intravenously.

3. For agitation—10 ml of a 25% magnesium sulfate solution administered intramuscularly.

4. Forced diuresis.

Symptoms of poisoning by panther cap (Amanita pantherina) or grey spotted amanita (Amanita porphyria) typically appear 1-2 hours after ingestion. Manifestations include nausea, vomiting, mucosal dryness, fever, mydriasis, and tachycardia (resembling atropine poisoning). Severe cases are characterized by psychomotor agitation, euphoria, hallucinations, Muscle fibrillations, and twitching.

Treatment. 1. Immediate gastric lavage via tube, followed by the administration of a saline laxative.

2. Forced diuresis.

3. For psychomotor agitation: 2.5% chlorpromazine solution (12 mL in 20 mL of 40% glucose solution intravenously).

4. Prosergine 1-2 mL of 0.05% solution subcutaneously, pilocarpine hydrochloride 1% - 1 mL subcutaneously.

Poisoning by true morels (Morchella). Morels contain a toxin (helvellic acid) that exhibits hemolytic and hepatotoxic effects. Helvellic acid is readily soluble in hot Water; therefore, preliminary rinsing and thorough boiling at t° 80-100 °C render the mushrooms edible. The water used for boiling and washing the mushrooms must not be used for cooking.

When improperly prepared morels are consumed, poisoning symptoms appear within 6-10 hours, sometimes up to 24 hours. Clinical signs include nausea, vomiting, abdominal pain, jaundice of the sclera and Skin, hepatosplenomegaly, erythrocyte hemolysis, and possible convulsions. Death occurs on the 3rd to 4th day due to hepatorenal and cardiac failure, frequently preceded by a comatose state.

Treatment. 1. Gastric lavage, administration of activated charcoal (2 tablespoons per 0.5 L of water).

2. For severe agitation: 2.5% chlorpromazine solution 1-2 mL.

3. Hemodialysis During the first 24 hours post-ingestion.

4. Choline chloride - 20% solution (dilute 2 ampoules in 200-300 mL of isotonic sodium chloride solution or 5% glucose solution, administered as an intravenous drip at 30 drops/min).

5. Glucocorticoids (prednisolone 90-180 mg (up to 1000 mg/day) during the first days of treatment.

6. Glutamic acid 1% solution 20-30 mL with 500 mL of 10% glucose solution administered as an intravenous drip.

7. Lipoic Acid (100-200 mg/day intravenously) or lipamide (500-800 mg/day).