Intoxication of the body: symptoms and diagnosis

Intoxication of the body almost always accompanies a serious trauma and in this sense is a universal phenomenon, which, from our point of view, has not always been given enough attention. In addition to the word "intoxication", the term "toxicosis" is often found in the literature, which includes the notion of the accumulation of toxins in the body. However, in strict interpretation, it does not reflect the body's response to toxins, that is, poisoning.

Even more controversial in terms of semantics is the term "endotoxicosis", meaning the accumulation of endotoxins in the body. If we consider that endotoxins are called toxins from bacteria, it turns out that the term "endotoxicosis" should be applied only to those types of toxicosis that are of bacterial origin. Nevertheless, this term is used more widely and it is used even when it is a matter of toxicosis on the basis of endogenous formation of toxic substances not necessarily associated with bacteria, but appearing, for example, as a result of metabolic disorders. This is not entirely correct.

Thus, to denote the poisoning accompanying severe mechanical trauma, it is more appropriate to use the term "intoxication", which includes the concept of toxicosis, endotoxicosis and the clinical manifestations of these phenomena.

The extreme degree of intoxication can lead to the development of toxic or endotoxic shock, which arise as a result of excess of the adaptive capacity of the organism. In conditions of practical resuscitation, toxic or endotoxic shock most often complete crash syndrome or sepsis. In the latter case, the term "septic shock" is often used.

Intoxication in severe shockogenic trauma occurs early only in those cases when it is accompanied by large crushing of tissues. However, on average, the peak of intoxication falls on 2-3 days after the trauma and it is at this time that its clinical manifestations, which in aggregate constitute the so-called intoxication syndrome, peaked .

[1], [2], [3]

Causes of the intoxication of the body

The notion that intoxication always accompanies a severe trauma and shock appeared at the beginning of this century in the form of the toxical theory of traumatic shock proposed by P. Delbet (1918) and E. Quenu (1918). A lot of evidence in favor of this theory was presented in the writings of the famous American pathophysiologist W. V. Cannon (1923). The basis of the theory of toxemia lay the fact of the toxicity of the hydrolysates of the crushed muscles and the ability of the blood of animals or patients with traumatic shock to retain toxic properties when administered to a healthy animal.

The search for a toxic factor that was intensively produced in those years led to nothing, except for the works of N. Dale (1920), who found histamine-like substances in the blood of shock victims and became the founder of histamine shock theory. His data on hyperhistaminemia in shock were confirmed later, but the monopathogenetic approach to the explanation of intoxication in traumatic shock was not confirmed. The fact is that in recent years a large number of compounds formed in the body with trauma have been discovered, which claim to be toxins and are pathogenetic factors of intoxication in traumatic shock. A picture of the origin of toxemia and its accompanying intoxication began to be depicted, which is connected, on the one hand, with a multitude of toxic compounds formed during trauma, and on the other - due to endotoxins of bacterial origin.

The overwhelming majority of endogenous factors are associated with protein catabolism, which increases significantly with a shockogenic injury and averages 5.4 g / kg-day at a rate of 3.1. Especially pronounced decomposition of muscle protein, increasing in 2 times in men and in 1.5 times in women, as muscle hydrolysates are particularly toxic. The threat of poisoning is the products of protein decay in all fractions, from high molecular weight to the final products: carbon dioxide and ammonia.

Speaking of protein splitting, any denatured protein in the body, which has lost its tertiary structure, is identified by the body as alien and is the object of attack by phagocytes. Many of these proteins that appear as a result of trauma or tissue ischemia become antigens, ie, the bodies to be removed, and are able, by virtue of their redundancy, to block the reticuloendothelial system (RES) and lead to a detoxification deficiency with all the ensuing consequences. The most serious of them is a decrease in the body's resistance to infection.

A particularly large number of toxins are found in the mid-molecular fraction of polypeptides formed as a result of protein breakdown. In 1966, AM Lefer and C. R. Baxter independently described the myocardial depressant factor (MDF), formed during shock in the ischemic pancreas and representing a polypeptide with a molecular weight of about 600 daltons. In the same fraction, toxins that caused depression of RES were found, which turned out to be annular peptides with a molecular weight of about 700 daltons.

A higher molecular weight (1000-3000 daltons) is determined in a polypeptide formed in the blood in shock and causing lung damage (this refers to the so-called adult respiratory distress syndrome - RDSV).

American researchers A. N. Ozkan et al. In 1986 they reported the discovery in the blood plasma of polytraumatized and burn patients with glycopeitis with immunosuppressive activity.

Interestingly, in some cases, toxic properties are acquired by substances that perform physiological functions under normal conditions. An example can be endorphins belonging to the group of endogenous opiates, which, with excess formation, can act as a means of suppressing respiration and causing inhibition of cardiac activity. Especially a lot of such substances are found among low-molecular protein products. Such substances can be called facultative toxins, in contrast to obligate toxins, which always have toxic properties.

Toxins of protein origin

Toxins	Who was found	Types of shock	Origin	Molecular mass (dalton)
MDF Lefer	Man, cat, dog, monkey, guinea pig	Hemorrhagic, endotoxin, cardiogenic, burn	Pancreas	600
Williams	Dog	Blockage of the superior mesenteric artery	Intestine
PTLF Nagler	The man, the rat	Hemorrhagic, cardiogenic	Leukocytes	10,000
Goldfarb	Dog	Hemorrhagic, splanchnic ischemia	Pancreas, planchettal zone	250-10,000
Haglund	Cat, rat	Splanchnic ischemia	Intestine	500-10 000
Mс Conn	Human	Septic	-	1000

An example of facultative toxins in shock can be considered histamine, formed from the amino acid histidine, and serotonin, which is a derivative of another amino acid - tryptophan. Some researchers attribute to the optional toxins and catecholamines formed from the amino acid phenylalanine.

Significant toxic properties are the final low-molecular decay products of the protein - carbon dioxide and ammonia. First of all, this refers to ammonia, which even in a relatively low concentration causes a breakdown in the function of the brain and can lead to coma. However, despite the increased formation of carbon dioxide and ammonia in the body in shock, hypercarbia and ammoniaemia do not seem to have much significance in the development of intoxication due to the presence of powerful systems for neutralizing these substances.

Among the factors of intoxication are also peroxide compounds, formed during a shock injury in significant quantities. Usually, redox reactions in the body consist of fast-flowing stages on which unstable but very reactive radicals are formed, such as superoxide, hydrogen peroxide and OH "radical, which have a pronounced damaging effect on the tissue and thus lead to protein breakdown. In shock, the transience of oxidation-reduction reactions decreases and, at its stages, the accumulation and isolation of these peroxide radicals takes place. Another source of their formation may be neutrophils, which release peroxides as a microbicidal agent as a result of increasing their activity. The peculiarity of the action of peroxide radicals lies in the fact that they are able to organize a chain reaction involving lipid peroxides formed as a result of interaction with peroxide radicals, after which they become a factor of tissue damage.

Activation of the described processes, observed during a shock injury, is, apparently, one of the serious factors of intoxication in shock. This is indicated by the data of Japanese researchers who, in animal experiments, compared the effect of intra-arterial administration of linoleic acid and its peroxides at a dose of 100 mg / kg. In observations with the introduction of peroxides, this resulted in a 50% decrease in the cardiac index 5 min after injection. In addition, the total peripheral resistance (OPS) increased, pH and excess of the base of blood were markedly reduced. In dogs with the introduction of linoleic acid, changes in the same parameters were insignificant.

One more source of endogenous intoxication should be mentioned, for the first time in the mid-1970s. Drew attention to R. M. Hardaway (1980). This is an intravascular hemolysis, with the toxic agent being not the free hemoglobin moving from the erythrocyte to the plasma, but the erythrocytic stroma, which, according to R. M. Hardaway, causes intoxication due to proteolytic enzymes localized on its structural elements. MJ Schneidkraut, DJ Loegering (1978), who investigated this issue, found that the stroma of red blood cells is very quickly withdrawn from the circulation by the liver, which in turn leads to depression of the RES and phagocytic function in hemorrhagic shock.

At a later date after the injury, an important component of intoxication is the poisoning of the body with bacterial toxins. At the same time, the possibility of both exogenous and endogenous intake is allowed. In the late 50's. J. Fine (1964) for the first time suggested that intestinal flora under the conditions of a sharp weakening of the function of RES at shock can cause a large number of bacterial toxins to enter the circulation. This fact was later confirmed by immunochemical studies, which revealed that with various types of shock in the blood of the portal vein, the concentration of lipopolysaccharides, which are the group antigens of intestinal bacteria, increases significantly. Some authors believe that by nature endotoxins are phosphopolysaccharides.

So, the ingredients of intoxication in shock are numerous and heterogeneous, but the overwhelming majority of them have an antigenic nature. This applies to bacteria, to bacterial toxins and to polypeptides, which are formed as a result of protein catabolism. Apparently, other substances with a lower molecular weight, being haptens, can serve as antigen by combining with a protein molecule. In the literature devoted to the problems of traumatic shock, there are data on the excessive formation of auto- and heteroantigens in severe mechanical trauma.

In the conditions of antigenic overload and functional blockade of RES in case of severe trauma, the incidence of inflammatory complications increases, proportional to the severity of trauma and shock. The incidence and severity of inflammatory complications correlates with the degree of impairment of the functional activity of different populations of blood leukocytes as a result of exposure to mechanical trauma. The main reason is obviously related to the action of various biologically active substances in the acute period of the trauma and the disturbance of metabolism, as well as the effect of toxic metabolites.

[4]

Symptoms of the intoxication of the body

Intoxication with a shock trauma is characterized by a variety of clinical signs, many of which are not specific. Some researchers attribute to them indicators such as hypotension, frequent pulse, rapid breathing.

However, based on clinical experience, it is possible to identify the signs that have a closer connection with intoxication. Among these signs, the greatest clinical significance is encephalopathy, thermoregulatory disorders, oliguria and dyspeptic disorders.

Usually, the victims with traumatic shock intoxication develops against the background of other signs characteristic of a shock injury, which can enhance its manifestations and severity. Such signs include hypotension, tachycardia, tachypnea, and so on.

Encephalopathy refers to reversible disorders of the functions of the central nervous system (CNS), arising from the effects of circulating toxins in the blood on the brain tissue. Among a large number of metabolites, ammonia plays an important role in the development of encephalopathy - one of the final products of protein catabolism. It has been established experimentally that intravenous administration of a small amount of ammonia leads to a rapid development of the cerebral coma. This mechanism is most likely in traumatic shock, since the latter is always accompanied by an increased disintegration of proteins and a decrease in the detoxification potential. The development of encephalopathy is associated with a number of other metabolites, formed in high amounts in traumatic shock. G. Morrison et al. (1985) reported that they studied the fraction of organic acids whose concentration is significantly increased with uremic encephalopathy. Clinically, it manifests itself as adynamia, pronounced sleepiness, apathy, lethargy, indifferent attitude of patients to the surrounding. The growth of these phenomena is associated with loss of orientation in the situation, a significant decrease in memory. Severe degree of intoxication encephalopathy can be accompanied by delirium, which, as a rule, develops in the victims who abused alcohol. In this case, clinical intoxication manifests itself in a sharp motor and speech excitement and complete disorientation.

Usually, the degree of encephalopathy is assessed after communication with the patient. Isolate mild, moderate and severe encephalopathy. For an objective assessment of it, judging from the experience of clinical observations in the departments of the Institute of First Aid Im. II Janelidze, you can apply the Glasgow coma scale, which was developed in 1974 by G. Teasdale. Its use makes it possible to parametrically assess the severity of encephalopathy. The advantage of the scale is the regular reproducibility, even when it is calculated by the average medical personnel.

At intoxication in patients with a shock trauma a decrease in the rate of diuresis is observed, the critical level of which is 40 ml per minute. Decrease to a lower level indicates oliguria. In cases of severe intoxication, complete cessation of urine output occurs and uremic encephalopathy joins the phenomena of toxic encephalopathy.

Scale Coma Glasgow

Speech response	Score	Motor response	Score	Opening the eyes	Score
Oriented Patient knows who he is, where he is, why he is here	5	Executing Commands	6th	Spontaneous Opens the eyes when the vestigecle is not always consciously	4
		Sensible pain response	5
Unclear conversation The patient answers questions in a colloquial manner, but the answers show a different degree of disorientation	4			He opens his eyes to the voice (not necessarily by command, but simply by voice)	3
		Distraction for pain, unreasoned	4
		Flexion to pain can vary either fast or slow, the latter being characteristic of a decorticated response	3	Opening or intensifying the closing of the eyes to the pain	2
Inconsistent speech Strong articulation, speech includes only exclamations and expressions combined with abrupt phrases and curses, can not support conversation	3
				No	1
		Extension to pain, decerebratic rigidity	2
		No	1
		Unintelligible speech It is defined in the form of moans and moaning	2
No	1

Dyspeptic disorders as manifestations of intoxication are much less common. Clinical manifestations of dyspeptic disorders include nausea, vomiting, and diarrhea. Most often, nausea and vomiting occur due to toxins of endogenous and bacterial origin circulating in the blood. Proceeding from this mechanism, vomiting during intoxication refers to hematogenous-toxic. It is characteristic that dyspeptic disorders during intoxication do not bring relief to the patient and occur as relapses.

[5]

Forms

[6], [7],

Crash Syndrome

The prevalence of toxicosis in the acute period is clinically manifested in the form of the development of the so-called crash syndrome, which was described by NN Elanskii (1950) in the form of traumatic toxicosis. Usually this syndrome accompanies the crushing of soft tissues and is characterized by the rapid development of consciousness disorders (encephalopathy), a reduction in diuresis up to anuria and a gradual decrease in the level of arterial pressure. The diagnosis, as a rule, does not cause any special difficulties. Moreover, by the type and localization of the crushed wound, the development of the syndrome and its outcome can be predicted quite accurately. In particular, crushing of the thigh or its detachment at any level leads to the development of fatal intoxication in the event that amputation is not performed. Crushing injury of the upper and middle third of the lower leg or the upper third of the shoulder is always accompanied by severe toxicosis, which can still be managed under the condition of intensive treatment. Crushing more distal segment limbs is usually not so dangerous.

Laboratory data in patients with crash syndrome are quite typical. According to our data, the greatest changes are typical for the level of SM and LII (0.5 ± 0.05 and 9.1 ± 1.3, respectively). These indicators reliably distinguish patients with crush syndrome among other victims with traumatic shock, who had significantly different levels of CM and LII (0.3 ± 0.01 and 6.1 ± 0.4). 14.5.2.

[8], [9], [10],

Sepsis

Patients who have undergone an acute period of traumatic illness and accompanying early toxicosis may then again find themselves in a serious condition due to the development of sepsis, which is characterized by the attachment of intoxication of bacterial origin. In most cases, it is difficult to find a clear time boundary between early toxicosis and sepsis, which in patients with trauma usually constantly shift into each other, creating a mixed pathogenetic symptom complex.

In the clinical picture of sepsis, severe encephalopathy remains, which, according to RO Hasselgreen, IE Fischer (1986), is reversible dysfunction of the central nervous system. Its typical manifestations consist of agitation, disorientation, which then turn into stupor and to whom. Two theories of the origin of encephalopathy are considered: toxic and metabolic. In the body, sepsis produces myriad toxins, which can have a direct effect on the central nervous system.

Another theory is more specific and proceeds from the fact of increased formation in sepsis of aromatic amino acids that are precursors of such neurotransformers as noradrenaline, serotonin, dopamine. Derivatives of aromatic amino acids displace neurotransmitters from synapses, which leads to disorganization of the central nervous system and the development of encephalopathy.

Other signs of sepsis - hectic fever, depletion with the development of anemia, multi-organ failure are typical and usually accompanied by characteristic changes in laboratory data in the form of hypoproteinemia, high levels of urea and creatinine, elevated levels of CM and LII.

A typical laboratory sign of sepsis is the positive result of blood culture. Doctors who interviewed six centers of trauma around the world found that the most constant criterion of sepsis is precisely this symptom. The diagnosis of sepsis in the post-shock period, based on the above indicators, is very responsible primarily because this complication of the injury is accompanied by a high level of lethality - 40-60%.

The toxic shock syndrome (TSS)

The toxic shock syndrome was first described in 1978 as a severe and usually fatal infectious complication caused by a specific toxin produced by staphylococcus aureus. It occurs with gynecological diseases, burns, postoperative complications, etc. STS manifests itself clinically in the form of delirium, significant hyperthermia, reaching 41-42 ° C, accompanied by headache, abdominal pain. Characteristic diffuse erythema of the trunk and hands and a typical language in the form of the so-called "white strawberries."

In the terminal phase, oliguria, anuria develops, and sometimes a syndrome of disseminated intravascular coagulation with hemorrhages into the internal organs joins. The most dangerous and typical is a brain hemorrhage. The toxin that causes these phenomena is found in staphylococcal effluents in approximately 90% of cases and is called toxin of toxic shock syndrome. Defeat toxins are found only in those people who are not able to produce the appropriate antibodies. Such an inactivity occurs in about 5% of healthy people, apparently, only people with a weak immune response to staphylococcus become ill. When the process progresses, anuria appears and a lethal outcome quickly occurs.

Diagnostics of the intoxication of the body

To determine the severity of intoxication in shockogenic trauma, various methods of laboratory analysis are used. Many of them are widely known, others are less commonly used. However, from the numerous arsenal of methods it is still difficult to single out one that is specific for intoxication. The following are methods of laboratory diagnosis, which are the most informative in determining intoxication in victims with traumatic shock.

The leukocyte index of intoxication (LII)

It was proposed in 1941 by J. Ya. Kalf-Kalifom and is calculated as follows:

LII = (4Mu + 3NO2n + C) • (Pl + 1) / (A + Mo) • (E + 1)

Where My - myelocytes, Yu - juveniles, P - bacillary leukocytes, C - segmented leukocytes, Pl - plasma cells, L - lymphocytes, Mo - monocytes; E - eosinophils. The number of these cells is taken as a percentage.

The meaning of the indicator is to take into account the cellular reaction to the toxin. The normal value of the LII indicator is 1.0; when intoxication in victims with a shock injury it increases by 3-10 times.

The level of average molecules (CM) is determined colorimetrically according to NI Gabrielian et al. (1985). Take 1 ml of blood serum, treat with 10% solution of trichloroacetic acid and centrifuge at a speed of 3000 rpm. Then 0.5 ml is taken over the sediment and 4.5 ml of distilled water and measured on a spectrophotometer. The SM index is informative in assessing the degree of intoxication, it is considered its marker. The normal value of the CM level is 0.200-0.240 uel. Units With an average degree of intoxication, the level of CM = 0.250-0.500 uel. Units, with heavy - more than 0.500 uel. Units

Determination of serum creatinine. Of the existing methods for determining serum creatinine, the FV Pilsen, V. Boris method is now more often used. The principle of the method is that picric acid interacts with creatinine in an alkaline medium with the formation of an orange-red color, the intensity of which is measured photometrically. The determination is made after deproteinization.

Creatinine (μmol / L) = 177 A / B

Where A is the optical density of the sample, D is the optical density of the reference solution. Normally, the level of serum creatinine is 110.5 ± 2.9 μmol / l.

[11],

Determination of the filtration pressure of blood (FDC)

The principle of the technique proposed by RL Swank (1961) is to measure the maximum level of blood pressure that provides a constant volumetric rate of blood flow through the calibrated membrane. The method in the modification of NK Razumova (1990) consists in the following: 2 ml of blood with heparin (at the rate of 0.02 ml of heparin per 1 ml of blood) is mixed and the filtration pressure in physiological solution and in blood is determined on a device with a roller pump. The FDC is calculated as the difference in filtration pressures of blood and solution in mm Hg. Art. The normal value of FDC for human heparinized blood is an average of 24.6 mm Hg. Art.

Determination of the number of floating particles in blood plasma (according to the method of NK Razumova, 1990) is performed in the following way: 1 ml of blood is taken to a degreased tube containing 0.02 ml of heparin and centrifuged at 1500 rpm for three minutes, then the resulting plasma was centrifuged at 1500 rpm for three minutes. For analysis, take 160 μl of plasma and dilute 1: 125 with saline. The resulting suspension is analyzed on a telescope. The number of particles in 1 μl is calculated by the formula:

1.75 • A,

Where A is the index of the celloscope. Normally, the number of particles in 1 μl of plasma is 90-1000, in those with traumatic shock - 1500-1600.

[12], [13], [14], [15], [16]

The degree of hemolysis of the blood

Severe injury is accompanied by the destruction of red blood cells, the stroma of which is the source of intoxication. For analysis, blood is taken with any anticoagulant. Centrifuge 10 minutes at 1500-2000 rpm. The plasma was separated and centrifuged at 8000 rpm. In a test tube, 4.0 ml of acetate buffer is measured; 2.0 ml of hydrogen peroxide; 2.0 ml of benzidine solution and 0.04 ml of test plasma. The mixture is prepared immediately before analysis. It is stirred and left to stand for 3 minutes. Then photometrize in a cuvette 1 cm against the compensation solution with a red light filter. Measure 4-5 times and record the maximum readings. Compensation solution: acetate buffer - 6.0 ml; hydrogen peroxide - 3.0 ml; solution of benzidine - 3.0 ml; saline solution - 0.06 ml.

Normal content of free hemoglobin 18.5 mg%, in patients with a shock injury and intoxication, its content increases to 39.0 mg%.

Determination of peroxide compounds (diene conjugates, malonic dialdehyde - MDA). Due to its damaging effect on the tissue, peroxide compounds, formed during a shock injury, are a serious source of intoxication. To determine them, 0.5 ml of plasma are added 1.0 ml of bidistilled water and 1.5 ml of cooled 10% trichloroacetic acid. The samples are mixed and centrifuged for 10 minutes at 6000 rpm. In test tubes with thin sections, 2.0 ml of supernatant are taken and the pH of each test and blank sample is adjusted to two with a 5% NaOH solution. The blank sample contains 1.0 ml of water and 1.0 ml of trichloroacetic acid. 

Ex tempore prepare a 0.6% solution of 2-thiobarbituric acid on bidistilled water and add 1.0 ml of this solution to all the samples. The tubes are closed with ground stoppers and placed in a boiling water bath for 10 minutes. After the sample is cooled, the photometry is immediately photometrated on a spectrophotometer (532 nm, 1-cm cuvette, against control). The calculation is made by the formula

C = E • 3 • 1.5 / e • 0.5 = E • 57.7 nmol / ml,

Where C is the concentration of MDA, normal MDA concentration is 13.06 nmol / ml, with shock - 22.7 nmol / ml; E - sample extinction; e is the molar extinction coefficient of the trimethine complex; 3 - volume of the sample; 1,5 - dilution of the supernatant; 0.5 - the amount of serum (plasma) taken for analysis, ml.

Determination of the index of intoxication (AI). The possibility of an integrated assessment of the severity of intoxication based on several indicators of protein catabolism was almost never used, primarily because it was unclear how to determine the contribution of each of the indicators to the severity of toxicosis. The doctors attempted to rank the alleged signs of intoxication depending on the actual consequences of the trauma and its complications. Denoting by the index (-T) the life expectancy in the days of patients with severe intoxication, and the index (+ T) - the duration of their stay in the hospital, it was then possible to establish correlation links between the indicators pretending to be the criteria for the severity of intoxication in order to determine their contribution in the development of intoxication and its outcome.

Treatment of the intoxication of the body

The analysis of the correlation matrix made during the development of the prognostic model showed that of all the indicators of intoxication, the maximal correlation correlation with the outcome is precisely in this indicator, the highest values of AI were observed in the dead patients. Convenience of its use is that it can be a universal sign when determining indications for extracorporeal methods of detoxification. The most effective detoxification measure is the removal of crushed tissues. If the upper or lower extremities are crushed, then it is a question of primary surgical treatment of the wound with maximum excision of the destroyed tissues or even of amputation, which is performed in an emergency. If it is impossible to excise the crushed tissues, a complex of local detoxification measures is performed, including surgical treatment of wounds and the use of sorbents. When suppurating wounds, which are often the primary source of intoxication, detoxification therapy also begins with a local effect on the focus - secondary surgical treatment. The peculiarity of this treatment is that the wounds, like in the case of primary surgical treatment, are not sewn and are drained after it is carried out. If necessary, flow drainage using various bactericidal solutions is used. The most effective use of a 1% aqueous solution of dioxidine with the addition of broad-spectrum antibiotics. In the case of insufficient evacuation of contents from the wound, drainage with active aspiration is used.

In recent years, sorbents used locally have been widely used. On the wound, activated charcoal is applied in the form of powder, which is removed after several hours, and the procedure is repeated again.

More promising is the local use of membrane devices that provide a controlled process for the introduction of antiseptics into the wound, analgesics and the removal of toxins.