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by Gennady POROSHENKO, Dr. Sc. (Biol.), Head of Department of the Scientific Research Institute of General Reanimatology, Russian Academy of Medical Sciences (Moscow)
Doctors today have everything they need-technical equipment and technological procedures (developed mainly thanks to the studies of Academician Vladimir Negovsky, Member of the USSR Medical Academy and founder of Russian reanimatology) which can bring a patient back to life after a cardiac arrest. It is a much more difficult problem trying to restore the normal "interior" of a patient so as to bring him back to normal productive life. It is therefore only natural that most of the studies by our Institute specialists are focused on this problem.
Irrespective of what could be the cause leading to a critical condition of a patient with a lethal outcome* (lesion of a major artery with a massive loss of blood, acute craneocerebral trauma, bullet wound, infection, cardiac fibrillation, difficult childbirth, etc.) the main cause of the crisis is hypoxia produced by arrest of breathing and blood circulation-arrest of oxygen supply to the vital organs of a patient.
All vital processes are based on a mechanism of transition of a free electron from hydrogen to oxygen which takes place on mitochondria membranes-tiny components of a cell produced by Mother Nature for that purpose. Produced as a result is the main "carrier" of energy of the organism-adenosine triphosphoric acid. That is why the first thing to do in dealing with such patients is trying to restore their breathing and heartbeat. Thanks to such efforts the vital "source of life" is supplied to the cells and tissues of a patient. But in the conditions of upsets of the general regulation mechanisms, homeostasis, and intercellular interaction on the initial stages of such interventions it can do more harm than good. There begins in tissues active formation of free radicals which rapidly turns into a kind of chain reactions. Mechanisms of dangerous processes are activated producing what we call post-reanimation complications or illness. Dealing with it is quite a problem for medical practitioners and is therefore the key area of the corresponding theoretical studies.
And it is the duty of a doctor not only to restore, but also ensure the sufficient supply of oxygen to body organs and tissues, especially in patients with acute respiratory insufficiency. Dealing with this problem is therefore one of the vital tasks of reanimatologists - a problem which is being dealt with the help of what we call mechanical ventilation of lungs. The latest studies at our Institute indicate that in patients with lesions of the main functional tissue of these organs the treatment should be started (with simultaneous volume control) with choosing an optimal for each individual case of "positive" pressure at the end of expiration.
While actively pumping in the gas mixture into the lungs, one should not forget about the danger of distension of alveoli, upsets of venous discharge and lymphodynamics. Our Institute scientists have carried out
* See: G. Poroshenko, "Medicine of Critical States", Science in Russia, No. 5, 2004 - Ed.
studies for the optimization of the methods and parameters of respiratory support. Their results indicate that the priority criterion in such cases is the mean pressure in the lungs. It can be controlled by the length of final inspiratory (after inhalation) pause and positive pressure at the end of exhalation and one-minute breath volume.
At the next stage of treatment there comes the problem of the independent performance of this function by patients. For its successful implementation there are several tests of different importance not all of which, unfortunately, can be applied in different conditions. Therefore scientists from the Institute of General Reanimatology of the Russian Medical Academy have carried out manifold tests and suggested that for predicting the possibility of reducing breathing support for patients with damaged functional lung tissue, it is possible to use pressure developed by them at the end of the first 100 ms of the usual exhalation. This method is the most sensitive, authentic and can be used in any conditions.
What is necessary, however, is not only to supply the lungs of a patient with oxygen, but also to overcome the aftermath of hypoxia which most of all affects the nervous system. Its restoration therefore is the main and most complicated problem whose solution requires in-depth studies of the pathological and compensatory changes developing in the organism during that period. Out of all the elementary living structures it is the neurons which consume the largest volume of oxygen. If this amount is reduced by 1.5 - 2 times, the cell metabolism is sharply reduced which affects the bioenergetics of the cerebral cortex, suppresses biosynthesis and activates necrosis of tissues (due to upsets of circulation).
Specialists of our Institute recently established that in critical conditions there are observed considerable upsets of the cytoplasma network - the intercellular membrane system responsible for protein synthesis. Among other things the penetrability is increased of the barrier which protects the brain from the penetration of many toxins. In the grey matter of dogs inspected after hemorrhagic shock by the 4th hour of arterial hypotension there occurred deep physico-chemical restructuring of protein molecules. And the destructive changes in the core of the central section of the nervous system were more rapid than in the liver or hypothalamus.
After 10 - 15 min of cardiac arrest, when the external neurological status of the animals was restored, specialists detected changes of density and composition of brain neurons, of the intensity of protein synthesis in it, etc. These lesions are observed for up to 60 days, but end after 8 months and the condition of the test animal
Spontaneous DNA synthesis in healthy persons (1), in patients with acute pneumonia (2), with acute myocardial infarction (3).
is improved. During the post-reanimation period in rats, in the absence of visible neurological disorders, during one to 2 days after reanimation there begins dystrophic restructuring of neurons, which increases after 14 days, and their interactions with glia*. Visible at the same time are upsets in the processes of excitation-inhibition processes, of the normal balance of what we call the passive-defensive and orientation-investigatory motivations (inadequate responses to external factors).
The complexity and "heterogeneity" of such changes of the inborn and acquired forms of behavior proves that the vulnerability of the structural-functional systems of the brain responsible for the emotional-motivatory status, is different. It has been possible to compensate, fully or in part, deviations of this kind by means of a single injection of the mexidol (antioxidant) preparation and some regulatory medicines. This helped normalize many of their behavioral factors and improve results of training with positive stimulation.
Thus the main mechanisms of post-reanimation upsets of the integral brain activities-decline of its "volume of information" storage; prolonged excitability of the central nervous system; increased responsiveness to acute and chronic emotional-negative impacts; isolation from signals of different modality; disorders caused by prolonged effect of preparations administered at the very beginning of reanimation treatment.
Studies at the Institute of General Reanimatology of the Russian Medical Academy indicate that against the background of general intensive therapy, the conditions of a patient are characterized by clearly expressed reactions of the endocrinal system-increased releases of vasopressin**, excessive activation of the system hypothalamus-hypophysis-adrenal glands, sub-clinical forms of sugar diabetis, hypothyreosis, etc. Depending on the adaptive requirements of the organism these processes are either activated, or partially suppressed. This helps support the cardio-vascular activities, the water-electrolyte balance and the metabolic support of functions of the muscles, gastro-intestinal tract, etc. Also reduced are the secretion and effect of insulin, thyroid hormones (produced by thyroid gland) which optimizes the functions of mitochondria and reduces the needs for oxygen of an organism fighting for its survival. In other words, doctors help to "put into operation" all of its defense system. Balance of this kind is extremely
* Glia (neoroglia) - cells in the brain and the spinal cord filling in the space between neurons and capillaries. Protect and support neurons, and ensure reactive properties of nervous tissue. - Ed.
* Vasopressin - nerve hormone produced in hypothalamus. It gets into pituitary body and from it-into the blood. - Ed.
Changing levels of hormones during long male comas.
important in cases of hypoxia. Unfortunately it cannot be fully achieved in all cases.
One acute problem facing medics-practitioners is sepsis. In the United States, for example, they register 400 - 500 thous. such cases with the lethality remaining in the range of 30 - 90 percent. This grave disorder is regarded as a syndrome of systemic inflammatory response of organism to practically any injury. Body cells try to protect themselves by producing many biologically active substances (more than 200 of them are known by the present time). A considerable place among them is occupied by cytokins - factors of tumor necrosis, activation of thrombocytes, etc. (more than 30 have been described). These are usually present in the body in picomolar concentrations. But in cases of illness, when all systems are unbalanced, they are produced in large volumes, reaching pharmacological proportions.
This process often progresses in an avalanche manner, turning from protective into pathological one. And sooner or later it is joined by bacterial flora. Some of its "representatives" are also present in healthy organisms (normally, 10 bacterial ones per every normal cell). In many cases sepsis is caused by intra-hospital infections: after changes of patients microbes remain on the walls and equipment. In some cases microbes are brought by patients with different inflammations.
So, what is the mechanism of formation of the defense reaction under consideration? It begins with the "recognition" of the pathogenic microbe and progresses in three stages: appearance of foci of production of cytokins; discharges of certain volumes of them into blood and lymph; generalization of sepsis. The clinical picture of the latter - the interaction of molecular, biochemical and cell processes-is very complicated. In most acute cases body mechanisms which control its response to bacterial "aggression" are upset and "excessive" inflammation takes place. This can cause damage at the level of cells and then organs and soon lead to the syndrome of polyorganic insufficiency.
The most dangerous complication in such cases is septic shock. Direct and indirect action of bacterial toxins promotes the development in such patients of upsets of blood circulation because of difference of hydrostatic pressure in different sections of circulatory system. This is accompanied by a depression of cardiac contraction, blocking of protein-cellular structures of the capillary alveus, etc. leading to upsets of the general and peripheral blood circulation and consequently, of oxygen transport and development of tissue dismetabolism and hypoxia. For practicing medics the signals of such disorders are increased palpitation, changing resistance of lung vessels, reduced arterial pressure and
general peripheral resistance, development of cardiac insufficiency, etc.
In dealing with sepsis one has to adopt a comprehensive approach. Its main components have been identified at our Institute. They include early diagnostics of the source of infection and, if possible, its sanation; antibacterial therapy (empirical with subsequent corrections according to data of bacteriological tests); introduction of hormones participating in metabolism and "adaptive" reactions; "prosthesis" of organs functions (artificial lung ventilation, blood purification, etc.) and correction of immune disorders. And the sooner such pathologies are identified together with the source of infection and curative procedures are started, the greater are the chances for a rapid recovery of the patient.
The reproductive functions of patients in critical conditions are suppressed. But the secretion of certain hormones engaged in the regulation of vital functions is increased irrespective of sex. Our specialists investigated by radioimmune and immuno-luminescent methods the hormonal profile of plasma of 170 males and females from 16 to 68 years of age after heavy skeletal injuries and losses of blood. The analysis of 15 hormones in their blood confirmed rapid development of endocrinal changes. These depend on the size of lesion, the condition of the patient and the effectiveness of therapy. Tendencies for normalization became apparent after 5 to 7 days of treatment.
It should be pointed out that using sex steroids (variety of organic compounds) in curing critical conditions is one of the promising trends of present-day reanimatology. This is because in the hierarchy of endocrinal systems the aforesaid hormones occupy the pride of place due to implementation of the central objective of living nature-self-support, self-preservation and self-development; reproduction; maintenance of social status.
At the present time our Institute scientists are working under the leadership of the Corresponding Member of the Medical Academy, Victor Moroz on the development of a new branch of medicine-prosthesis of functions. For many years now surgery, and later transplantology, have been working on methods of replacement of failed body structures, including transplantations of the heart, liver and kidneys. Significant progress has already been made, but there are still many problems connected with the search of appropriate donors, his immunological compatibility with the recipient, accumulating a bank of organs, etc.
Reanimatology approached the problem from another side-it started what they call "prosthesis of functions". For example in most patients in critical condition lungs are affected and have to be switched to mechanical ventilation. Very often in such situations it is necessary to control the functioning of the heart, even use artificial circulation. At the same time such patients often accumulate large volumes of poisonous substances produced by metabolic disorders. These are usually "deactivated" by the liver, but in many cases it is overloaded especially in people with alcoholic abuses, or patients after hepatitis, or chemical or biological poisoning (as from mushrooms). That makes it necessary to clean patients' blood with the help of special devices.
And there is another problem associated with the first one: with the help of kidneys harmful substances and products of their processing by the liver have to be evacuated with urine. But at certain concentrations of them the filtering role of the aforesaid organs is reduced to the minimum. Patients develop uremia-self-poisoning of the body which makes it necessary to use artificial kidneys. The battle with acute infections causing sepsis must also be joined by medics. In a word, vital mission of reanimotologists involves the prosthesis of the functions of the lungs, the heart, liver, and kidneys, combetting inflammations caused by pathogenic bacteria, etc. The main difference of this method from organs replacement is their temporary nature: after body systems emerge from critical condition they gradually return back to normal and no longer need artificial support.
Development work on such technologies has been in progress over many years. But it was only recently that we recognized them as a separate branch of medicine. This calls for a new approach to the treatment of critical conditions (and to a number of concrete problems of the science dealing with human health). It calls for broadening of our studies of ways of developing the necessary equipment and promises new achievements not only in biology and therapeutical practice, but also medical instrument making.
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