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

Main types of acute poisoning and their treatment
Carbon monoxide poisoning

Carbon monoxide poisoning consistently holds one of the leading positions in Acute Poisoning statistics, both in domestic settings and within the Armed Forces during peacetime.

Carbon monoxide, or carbon monoxide gas, is a product of the incomplete combustion of carbon-containing substances. The Emergence of toxic CO concentrations is typically associated with the incomplete oxidation of carbon-containing Materials during combustion, artillery and mortar fire, and aerial bomb explosions. In explosion gases, carbon monoxide content can reach 50–60%. Furthermore, certain chemical compounds can release significant amounts of carbon monoxide when exposed to high temperatures.

The most common causes of poisoning include malfunctioning heating systems or violations of their operating rules, faulty internal combustion engines or their operation in enclosed spaces (garages, bays), as well as fires. Among military personnel, poisonings may be associated with breaches in the operation of military equipment (vehicles, tanks, artillery systems, aircraft, etc.).

Carbon monoxide is a colorless, odorless gas that is lighter than air. Poisoning occurs exclusively via the inhalation route. The toxicity of CO is determined primarily by its concentration in the air and the duration of exposure. Data on CO toxicity are presented in Table 5.4. CO is classified as a general toxicant.

Class="center">Table 5.4 Human Toxicity of CO (according to Henderson and Haggard, 1999)

The maximum allowable concentration in the air of working premises is 0.02 mg/L. Individuals suffering from anemia, avitaminosis, or nutritional dystrophy are more sensitive to the effects of CO. The toxicity of carbon monoxide increases under conditions of reduced partial pressure of oxygen and elevated ambient Temperature.

MECHANISM OF ACTION and Pathogenesis of poisoning. Upon entering the Lungs with inhaled air and subsequently passing into the bloodstream, CO forms a stable compound with Hemoglobin (Hb), yielding carboxyhemoglobin (HbCO). Biochemical systems containing divalent iron (Myoglobin, Cytochromes, peroxidases, and others) also react with it, causing a drastic reduction in the oxygen-carrying capacity of the Blood ("emic asphyxia" in old terminology) and tissue Hypoxia ("cellular asphyxia") accompanied by severe impairments in Central Nervous system function, Respiration, hemodynamics, and so forth.

The intensive formation of HbCO is driven by the Chemical Nature of Carbon Monoxide and its high affinity for Hb. Hemoglobin saturation with CO occurs 250–300 times faster than with oxygen, whereas the dissociation of HbCO proceeds approximately 3,600 times slower than that of oxyhemoglobin (HbO₂).

As is known, The Structure of hemoglobin is a tetrameric complex capable of sequentially binding four O₂ molecules. Each subsequent attachment of oxygen is facilitated by Conformational Changes in the complex in response to the prior binding of O₂. Following full saturation of Hb with oxygen, the release of even a single O₂ molecule induces further conformational shifts that promote the more rapid dissociation of the remaining gas. This phenomenon is termed "heme-heme" interaction. Such a property of hemoglobin ensures its rapid oxygen saturation in the lungs and an equally rapid (explosive) release of the gas in tissue capillaries.

Under conditions of intoxication, the attachment of even a single CO molecule to hemoglobin is accompanied by A change in protein conformation and a disruption of the "heme-heme" interaction. As a result, the association and dissociation of O₂ with hemoglobin are slowed down. This phenomenon is known as the Haldane effect (named after the British scientist who discovered the aforementioned phenomenon). The paradox of the situation lies in the fact that the oxygen concentration in the blood may be quite high, yet the release of the gas from hemoglobin is impeded, creating conditions for The Development of tissue hypoxia.

The formation of HbCO is an important, but not the sole, link in the pathogenesis of poisoning. It has been established that CO interacts with the iron in myoglobin, resulting in the formation of carboxymyoglobin and impaired oxygen supply to working Muscles. This is likely the primary cause of the profound muscular weakness experienced during poisoning. Since myoglobin acts as an O₂ depot in the body, carbon monoxide poisoning disrupts not only Oxygen transport but also its storage. The affinity of myoglobin for CO exceeds the corresponding value for O₂ by approximately 40 times.

Cytochrome c oxidase serves as a target for carbon monoxide, although its affinity for the poison is 10 times lower than for oxygen. It has been established that prolonged exposure to carbon monoxide, even at low concentrations, leads to the development of O₂ deficit in Tissues (emic hypoxia caused by HbCO formation). In such a situation, cytochrome c oxidase begins to bind with CO, leading to enzyme deactivation and the onset of tissue hypoxia.

Experiments have demonstrated the possibility of CO binding to the iron of cytochrome P-450, which is a cofactor of monooxygenase systems. The affinity of cytochrome P-450 for carbon monoxide differs only slightly from its affinity for O₂. These Enzymes play a critical role in the biotransformation of both xenobiotics and numerous endogenous substrates of peptide and non-peptide nature. Severe disruptions in metabolic processes under conditions of CO intoxication can be interpreted as impaired function of monooxygenase systems.

Clinical picture of acute poisoning. The clinical picture of acute CO poisoning is characterized, first and foremost, by symptoms of central nervous system damage. General cerebral disorders manifest as headaches localized in the temporal and frontal regions, frequently constrictive in character ("tight headband" sign), dizziness, and nausea in severe poisonings. Vomiting occurs, sometimes recurrent, followed by a loss of consciousness that can progress to a deep coma.

Bulbocerebellar disturbances are characterized by miosis, mydriasis, or anisocoria, though in most cases pupils are of normal size with a brisk reaction to light. Unsteady gait, impaired motor coordination, tonic convulsions, and spontaneous myofibrillations are observed.

The presence of pyramidal lesions is indicated by increased Muscle tone in the extremities, hyperactive and widened zones of tendon Reflexes, and the appearance of the Babinski and Oppenheim signs.

Special attention should be paid to the onset of hyperthermia, which is of central origin and regarded as one of the early signs of toxic cerebral edema—the most severe complication of acute carbon monoxide poisoning.

Psychiatric disorders frequently manifest as agitation or stupor. The agitated state is characterized by acute psychotic symptoms (disorientation, visual-auditory hallucinations, persecutory delusions). It is more typical of situations associated with emotional trauma to the victim (fires, bomb explosions, shell blasts, etc.). In cases of domestic carbon monoxide poisoning from motor vehicles, a state of stupor, sopor, or coma is typical.

In some cases, In addition to hemic and tissue hypoxia, Hypoxic hypoxia also develops, caused by inspiratory dyspnea of central origin and upper airway obstruction resulting from bronchorrhea and hypersalivation. Impairments of external respiration, along with tissue and hemic hypoxia, are accompanied by shifts in acid-base balance and the Development of Respiratory, followed by metabolic, acidosis.

Inhalation of high concentrations of carbon monoxide can cause sudden death occurring at the scene as a result of respiratory arrest and primary toxic collapse caused by the paralysis of the respiratory and vasomotor centers. In some instances of severe poisoning, a picture of Exotoxic Shock develops. In less severe injuries, a hypertensive crisis with pronounced tachycardia is observed.

ECG changes are nonspecific; signs of myocardial hypoxia and impaired Coronary Circulation are usually detected: the R wave decreases in all leads, particularly in chest leads, the S-T interval shifts below the isoelectric line, and the T wave becomes biphasic or negative. In severe cases, ECG signs of coronary circulation impairment resembling myocardial infarction are observed. These changes typically disappear rapidly as the General condition of the victims improves; however, in severe poisonings, coronarogenic ECG abnormalities may persist for up to 7–15 days or longer.

CO intoxication is frequently accompanied by trophic disorders, especially in cases where victims, due to rapid loss of consciousness, remain for extended periods in awkward positions with twisted and compressed limbs (positional trauma). In the Cytology/cytology/16.html">Early stages of Skin-trophic disorders, bullous dermatitis with localized skin hyperemia and subcutaneous tissue edema is observed. Sometimes trophic disorders follow the pattern of ischemic polyneuritis, manifesting as atrophy of individual muscle groups, sensory disturbances, and restricted limb function.

In severe cases, necrotic dermatomyositis develops, wherein indurations and infiltrates are observed on hyperemic skin areas, followed by tissue necrosis and the formation of deep ulcers. In particularly severe cases of dermatomyositis, myorenal syndrome may develop, manifesting as ACUTE RENAL FAILURE due to myoglobinuric nephrosis of varying severity.

If the poisoning occurred recently, the skin and visible mucous membranes acquire a bright red color caused by carboxyhemoglobin. The skin of victims experiencing pronounced hypoxia is typically cyanotic.

The severity of carbon monoxide poisoning is determined by the concentration of the poison and the duration of exposure. Data on the clinical manifestations of CO poisoning at various blood HbCO concentrations are presented in Table 5.5. Currently, toxicologists distinguish two clinical courses of acute CO poisoning: 1) delayed — with typical and euphoric clinical forms, and 2) fulminant — with apoplectic and syncopal forms.

Table 5.5 Clinical manifestations of CO poisoning at various blood HbCO concentrations

In mild poisoning (HbCO level of 10-30%), patients experience headaches, predominantly in the frontal and temporal regions, dizziness, tinnitus, shortness of breath, generalized weakness, nausea, and occasionally vomiting and fainting. A slight flush appears on the Cheeks, along with cyanosis of the mucous membranes; consciousness is usually preserved, reflexes are hyperactive, a tremor of outstretched hands is observed, along with a slight increase in respiratory rate, pulse, and a moderate rise in blood pressure. These symptoms disappear within a few hours after cessation of CO exposure, except for the headache, which may persist for more than a day.

In moderate poisoning (HbCO level of 30-40%), the aforementioned symptoms are more pronounced. Muscle weakness and adynamia are observed, being so severe that they can threaten the victim's life, as the individual is unable to cover even a short distance due to weakness and coordination impairment. Shortness of breath intensifies, the pulse becomes rapid, blood pressure drops, and bright red spots frequently appear on the face. Victims lose The ability to orient themselves in time and space, consciousness is confused, and complete loss of consciousness or memory lapses are possible.

Severe poisoning (HbCO level of 50-70%) is accompanied by a complete loss of consciousness and a comatose state, which can last for 10 hours or more. The skin and mucous membranes are initially bright red, then acquire a cyanotic tint. The pupils are maximally dilated. The pulse is rapid, blood pressure is sharply decreased. Respiration is impaired and may be intermittent in the Cheyne-Stokes pattern. Body temperature rises to 38—40 °C. Muscles are tense, and attacks of tonic or clonic-tonic convulsions are possible. Subsequently, a deep comatose state develops, and remaining in it for more than a day is an unfavorable prognostic sign.

Severe cases of CO poisoning on days 2–3 may be complicated by trophic disorders, the appearance of erythematous spots, subcutaneous hemorrhages, and vascular thrombosis.

The euphoric form is a variant of severe CO poisoning characterized by a relatively slow increase in hypoxia, the development of speech and motor agitation followed by a loss of consciousness, and impairments in respiratory and Cardiac Activity.

The Clinical forms of the fulminant variant of poisoning are the apoplectic and syncopal forms.

The apoplectic form develops upon brief inhalation of carbon monoxide at very high concentrations (over 10 g/m³). The victim quickly loses consciousness and dies within 3-5 minutes, following a brief bout of convulsions, due to paralysis of the respiratory center.

The syncopal form is characterized by predominant depression of the vasomotor center and The Heart. It manifests as a sharp drop in blood pressure, cerebral ischemia, pallor of the skin, rapid loss of consciousness, and pronounced spasm of peripheral vessels. The skin acquires a pale, waxy appearance. The victim dies within a few minutes.

First aid and Treatment. The basis of treatment for carbon monoxide poisoning at the stages of medical evacuation includes the following provisions: maximizing the proximity of medical care to the casualties, early application of Oxygen therapy and resuscitation measures (CPR). Primary assistance to victims is provided at the site of the poisoning.

Since hypoxia is the leading pathogenic link in carbon monoxide poisoning, combating it is the main direction of medical care for victims. Poisoned individuals should be evacuated from the gas-contaminated atmosphere as quickly as possible and brought out into fresh air.

The reduction of HbCO to non-toxic concentrations occurs most rapidly during HBO (hyperbaric oxygen therapy): a drop in HbCO from 50% to 20% takes 7 hours when breathing atmospheric air, 2 hours during insufflation of pure O₂ at atmospheric pressure, and 50 minutes when using O₂ under a pressure of 2.5 atm absolute.

Assistance to victims of CO poisoning should include the following measures:

- restoration of external respiration (toilet of the Oral Cavity and Upper Respiratory Tract, artificial pulmonary ventilation, reflex respiratory stimulation);

- cessation of further intake of the poison into the body;

- «early» Hyperbaric Oxygenation (HBO);

- symptomatic therapy aimed at restoring the Functions of various Organs and systems (primarily respiration, circulation, central nervous system), acid-base balance (ABB), Water-electrolyte balance (WEB), as well as metabolic correction.

In CO poisoning, oxygen therapy occupies a central place among therapeutic measures. At the beginning of the intoxication (in the toxicogenic phase), it can be considered specific (antidotal), and as the clinical picture of the poisoning unfolds (somatogenic phase), it acts as symptomatic therapy aimed at eliminating hypoxia. Mostઉસfrequently, isobaric oxygen therapy is used because it is technically easy to perform with appropriate equipment (DP-2, DP-9, GS-8, KI-3). Pure oxygen is recommended in the first hours after poisoning, followed by a 40-50% oxygen-air mixture thereafter. The most effective treatment method for CO poisoning, especially moderate and severe cases, is HBO, where oxygen is supplied under elevated pressure.

In acute moderate and severe carbon monoxide poisoning, the earliest possible administration of the CO antidote, acizol, is indicated. Acizol has the ability to improve the oxygen-transport FUNCTIONS OF BLOOD under conditions of acute CO poisoning. It is administered intramuscularly at a dose of 1.0 ml of a 6.0% solution (1 human-dose). Repeated administration of the antidote is possible after 1.5-2 hours.

Some authors classify treatment with cytochrome c at an average dose of 15-50 mg as part of Pathogenetic Therapy, along with oxygen therapy.

In addition, to accelerate the elimination of CO from the body, iron and cobalt preparations are used, as well as ultraviolet irradiation (UVI) with erythemal doses applied to the entire surface of the victim's body.

Part of the drug therapy for CO poisoning is symptomatic. Sedatives are indicated in cases of agitation, while for convulsive syndrome, slow intravenous administration of 50-100 ml of a 1% barbamil solution, intramuscular administration of 1 ml of a 1% phenazepam solution, or bretal, or 10 ml of a 25% magnesium sulfate solution is used. For sharp agitation and signs of Brain edema, a lytic cocktail is administered intramuscularly: chlorpromazine (2 ml of a 2.5% solution or haloperidol), fentanyl, diphenhydramine (Benadryl), or tavegil. The administration of morphine is strictly prohibited.

Respiratory impairment and airway obstruction due to bronchospasm are indications for the intravenous administration of 10 ml of a 2.4% euphylline (aminophylline) solution, inhalation of bronchodilators, etc.

In cases of severe intoxication and the development of coma, ice packs are applied to the HEAD or craniocerebral hypothermia is performed for the Prevention and treatment of cerebral edema; intravenous administration includes 40 ml of a 40% glucose solution with 4-6 ml of a 5% ascorbic acid solution and 8 IU of Insulin, 50-100 mg of prednisolone, 40-80 mg of furosemide, and 10 ml of a 10% calcium chloride (gluconate) solution. An important role in the treatment of intoxications is played by combating metabolic acidosis—80-100 ml of a 4% sodium bicarbonate solution is administered intravenously. To correct tissue METABOLISM disorders, 2-4 ml of a 6% thiamine bromide solution and 2-4 ml of a 5% pyridoxine hydrochloride solution are administered intravenously or intramuscularly (do not mix in the same syringe). Measures are taken to prevent and treat toxic pulmonary edema, and Antibiotics are prescribed in standard doses for the prevention of Pneumonia.