- Email: [email protected]
Some neurological aspects of reanimatology
189
Resuscifution. 19 (1990) 189-197 Elsevier Scientific Publishers Ireland Ltd.
International
Some neurological
Communication
aspects of reanimatology* V.A. Negovsky
Institute of General Reanimatology, AMS Moscow (U.S.S.R.)
Among medical sciences there has recently appeared another one, reanimatology, the science of resuscitation. This science is close to anesthesiology and to many other clinical and theoretical disciplines which to some measure have to deal with problems of dying and resuscitation of the body. The essence of this science is the study ‘of the regular patterns of dying and recovery of the vital functions of the body to provide more effective therapy of terminal states. The role of recovery of central nervous system functions in resuscitation of the body is so great that reanimatology can be called with good reason a neurological science. Therapy aimed at recovery of the brain function should be started simultaneously with measures to be taken to restore the function of the cardio-vascular system and respiration. Recovery of the body without revival of the brain should be considered as a defect of resuscitation. We consider the body revived only in case when all its functions are revived including the complete recovery of the higher brain functions. Reanimatology is closely connected with theoretical biology since it is difficult to imagine the creation of the general theory of life, the whole conception of its essence without considering the stage at which life ends. Historical data are also important in the investigation of the given problem. Study of the mechanisms of decay and recovery of the vital functions in the phylogenetic aspect, especially detection of the processes determining the more elevated resistance of some animals to the developing process of dying, is a most important route of investigation. Struggle for earlier recovery of the dying patient from a severe terminal state, especially coma, is the main aim of the successful outcome of resuscitation. Recovery of cortical regulation of physiological functions is the most effective method of maintaining the beginning revival of the body and compensation of those pathological disorders, i.e. those “failures” which had developed in the body in the process of dying and at the initial period of revival. Of course, it would be groundless to hope for the compensatory role of the higher brain functions, if blood loss was not replaced and severe metabolic disorders were not eliminated. *Address delivered by Dr. Negovsky at the International Symposium “Central Nervous System and PostResuscitation Pathology of Organism” which was held in Moscow on March 14-16, 1989. 0300-9572/90/$03.50 0 1990 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
190
Significance of compensation of somatic disorders in the reviving body for recovery of the brain is being studied in detail at our Institute. In other words, it is necessary first of all to help the brain to recover its functions, and then the nervous regulation of all the processes occurring in the reviving body will be regained. A very complicated problem of correlation of the processes of inhibition and stimulation of the central nervous system of the reviving body remains to be unsolved, and it is a subject of detailed study. The question is at what stage of resuscitation it is advisable to enhance or weaken one of the two mentioned processes to achieve a complete favourable and full recovery of brain functions. Studies into the mechanisms of genesis of hypoxic and post-hypoxic pathology of the brain have allowed us to reveal the whole complex of pathochemical factors participating in the formation of post-resuscitation encephalopathies. These include changes in the energy formation processes, disorders in protein and phospholipid metabolism, activation of proteolysis enzymes, and changes in the state of membrane systems of neurons. At present the following research is of primary importance: further study of the molecular mechanisms of neurohormonal regulation of metabolism and functional activity of the nervous tissue, investigation of the receptor apparatus connected with the effector systems of the cell, and the role of secondary mediators in the development of post-resuscitation encephalopathies. The functional potentials of the brain in the post-resuscitation period are to a considerable degree determined by a decrease in the synaptic pool, capacity for recovery of damaged islands of nerve cells, and intraneuronal contacts, and formation of the new ones. It has been established that in the early post-resuscitation period marked destructive changes in synapses are observed in the brain cortex of animals. Compensatory-adaptive processes are restricted by hypertrophy of the preserved synapses and by transformation of less mature forms into typical functionally mature contacts. Later on an intensive process of formation of new synapses takes place which promotes a more complete recovery of the integrative function of the brain. It has been established that following clinical death of various etiology and duration, activation of the protein synthetizing apparatus of neurons occurs in response to severe hypoxia. This is evidenced by an increase in the size of the nucleus and cytoplasm of neurons, increase in their dry mass and in the size of the nucleolus of neurons. The degree of this process correlates with the duration of ischemia and the extent of recovery of the neurological status of animals. These results testify to the activation of the neurons protein-synthesizing apparatus during adaptation to severe hypoxia. It has been found that during the post-resuscitation period there occur profound changes in the structural and functional state of neuron chromatin, suggesting a possible change in the spectrum of synthesizing proteins. Such a shift may be regarded as one of the factors in formation of a post-resuscitation encephalopathy. The mechanism of such change require further study in the dynamics of the postresuscitation period. Affection of the central nervous system in the post-resuscitation period is caused
191
not only by direct action of hypoxia on the brain but also by a number of extracerebra1 factors. Elimination of endogenic intoxication in the early post-resuscitation period (methods of hemoperfusion, hemodialysis, ultrafiltration, plasmapheresis, plasmametabolism, donor circulation, use of xeno-organs) produces a marked favourable effect on the recovery of the central nervous system and sometimes even determines the outcome of resuscitation. Hemofiltration has proven very effective in patients with acute renal insufficiency which developed against the background of polyorgan insufficiency and sepsis. Hemofiltration, eliminating endotoxemia and correcting metabolic disorders in case of an early and intensive therapy promotes a reversal of coma, and improves treatment outcomes. It has been shown experimentally and clinically that elimination of toxic products helps to revive the brain, and quickens its recovery from the comatose state. Let me cite an instance of our latest observations: female patient Ya., 20 years old, case history N 1353, entered the resuscitation unit of the S.P. Botkin hospital in February 1987 in an extremely severe state, stage II-III coma, which had developed as a result of severe eclampsia, complicated by acute pulmonary insufficiency. The patient remained comatose for 28 days inspite of active therapy aimed at amelioration of cerebral circulation, brain metabolism, disintoxication and antioxidant therapy. During this period of time the apallic syndrome was being formed, the intercranial hypertension was being increased. The EEG-dominant was the slow 8rhythm of 4-5 oscillations/s. The mean molecules level in plasma of blood, determined by means of spectrophotometry of acid-dissolved plasma fractions, reached 0.500 conventional units. After 3 treatments of hemoperfusion, conducted consequently during 10 days, endogeneous intoxication decreased - the mean molecules level in blood plasma decreased to 0.270 conventional units. The patient showed signs of consciousness: she opened eyes when called, carried out simple instructions, but was quickly exhausted. The EEG showed that the past of slow waves considerably decreased, single and group a-oscillations appeared. One month later after the first hemoperfusion treatment the patient sat, held her head and back; her emotional reactions were adequate to the environment. Besides disintoxication therapy producing a favourable effect on the recovery of the central nervous system, hyperbarotherapy helping to regain the functions of the reviving brain is also worth of note. Scientific workers of our Institute have revealed that even after a postresuscitation comatose state lasting 2 months, hyperbaric therapy proved capable of evoking life in the brain which seemed to be dead. Let’s illustrate this fact with clinical observations: female patient B., 64 years old, case history N 2326, entered the S.P. Botkin Hospital on the 3rd of July, 1985. She suffered clinical death due serum sickness. To the end of the second month her state was characterized as apallic syndrome, tetraparalysis, spontaneous respiration and weak swallowing functions were preserved. The EEG showed the sharply flattened curve, tending to the isoline. The computerised tomography scanning showed the signs of internal and external hydroencephalopathy. After the first hyperbaric oxygenation (HBO) treatment swallowing functions improved. The EEG of both hemispheres showed the appearance of a-oscillations. On the next day by the beginning of the second treatment the EEG curve returned to its previous form (flat line), a-
192
activity disappeared. After the second HBO treatment obvious improvement was observed, the patient fixed eyes and followed with her eyes the object showed to her. The EEG again showed a-rhythm, which was firmly registered in the following days. After the third HBO treatment the signs of consciousness were observed. Later on consciousness was restored up to the verbal contact stage. Though only chaotic restoration of the nervous system functions was observed, these observations are valid from the point of view of positive effect of the HBO in the patient with apallic syndrome, which was irreversible according to all characteristics. At our Institute the question of neurologic therapy of reanimation patients has been worked out in detail by G.V. Alekseeva and her colleagues. I will touch upon only a few general principles of therapy conducted at the clinical department of our Institute. The fact that brain restoration has become the main task of modern reanimatology does not seem to be disputable. Restoration of the cardiac activity and respiration, and normalization of metabolic function help to revive the brain and reverse damage, caused by dying. But this is not sufficient. It is necessary to think about neurologic therapy aimed at restoration, of brain function, which should be prescribed from the moment of the patient’s entrance to the intensive care unit and should be continued periodically after the patient’s discharge (rehabilitation therapy). It is pertinent to remember that already in ancient times the three gates of death were known: not only heart and lungs, but brain as well. The following caveats appear true: -
-
Use of antihypoxants and then antioxidants is useful at the very early stage of treatment. It is necessary to support a sufficient level of blood pressure, as well as to use preparations which improve microcirculation in brain vessels. These act mainly as antiagregants. Medicamental pulmonary therapy by psychostimulating means (acephen, lucidril etc.) should be conducted when contraindications are absent. General strengthening therapy and is necessary.
As far as the use of barbiturates in patients who suffered clinical death is concerned, our earlier investigations have shown that barbiturates in certain dosage and at the certain stage of reanimation only in few cases have some positive effect. As a rule, they are ineffective. The recent investigations carried out at our Laboratory (mainly as a response to some positive evaluations of barbiturates in reanimation, which appeared in literature)* showed that both in experimental and clinical study the use of barbiturates, as a rule, becomes harmful after the brain has suffered severe hypoxia, i.e. clinical death. At the same time there is no doubt that barbiturates used before clinical death may be useful. One of the specific features of the terminal period is its contradictoriness. Many processes occurring in the terminal period often differ from the processes taking *See the chapter by P. Safar “Resuscitation Safar “Brain failure and resuscitation”.
after brain ischemia” in the book by A. Grenvik and P.
193
place in the living and even sick body and look like processes contradicting our general conceptions of life. In detailed study it becomes clear that these contradictions are not errors in cognition, or contradictions from the point of view of formal logits, but they do exist in reality and reflect the essence of this period of life. A seeming contradictoriness of a number of processes observed in dying and reviving of the body not infrequently brings some researchers to a deadlock. However, even Hegel wrote in his Logics: “. . . contradiction is a root of every movement of life, only because something has a contradiction in itself, it moves, possesses an impulse to activity”. * In this connection it is proper to quote a number of statements made by V.I. Lenin in his work “On the Question of Dialectics”. “Development is the struggle” of opposites. The two basic (or two possible? or two historically observable?) conceptions of development (evolution) are: development as decrease and increase, as repetition, and development as a unity of opposites (the division of a unity into mutually exclusive opposites and their reciprocal relation). In the first conception of motion, self-movement, its driving force, its source, its motive, remains in the shade (or this source is made external-God, subject, etc.). In the second conception the chief attention is directed precisely to knowledge of the source of “self)‘-movement. The first conception is lifeless, pale and dry. The second is living. The second alone furnishes the key of the “self-movement” of everything existing; it alone furnishes the key to the “leaps”, to the “break in continuity”, to the “transformation into the oppsite”, to the destruction of the old and the emergence of the new. The unity (coincidence identiy, equal action) of opposites is conditional, temporary, transitory, relative. The struggle of mutually exclusive opposites is absolute, just as development and motion are absolute”.** Returning to the analysis of the accumulated experience the following examples of contradictions of the terminal period features can be given: 1. Practice has shown it inadvisable and even dangerous to transfer the revived patient to natural breathing. One may object to this as it contradicts the generally accepted proposition concerning the use of natural breathing as a factor stimulating the reviving cortex. At the same time this contradiction exists in reality in life. And no logical error can be found in the above mentioned assertion. Life has shown that in the given situation one should not take into consideration the generally accepted proposition on the use of stimulation of the cortex, in particular, with impulses from the respiratory center that under other conditions may be undoubtedly of use, but should conduct long-term artificial ventilation, otherwise the patient may die. 2. It is common knowledge that comatose patients are given morphine. Some researchers may be confused by the use of morphine preparations for the given category of patients, as formally it contradicts the accepted and verified proposition on the usefulness of an early recovery of the patient from coma, as it is customary to *Hegel, “Science of Logics”, Collected Works, vol. 5, p. 520. Gos. Izd. of sotsio-ekonomic literature. **V.I. Lenin, Collected Works. “Philosophical Notebooks”, vol. 38, pp. 357-361, “Progress” Publishers, Moscow, 1976.
194
consider that morphine deepens coma. At the same time the usefulness of morphine preparations in comatose post-resuscitation patients has been proved by a great number of clinical observations. This actual contradiction can be explained by the fact that with administration of morphine pain impulses stop reaching the revived brain and, thus help its recovery from coma. The action of some other factors explaining this position is not excluded, though this is a contradictory phenomenon. 3. Revived patients may develop convulsions of the cental origin. The use of morphine also proved useful in this case. However, an objection may arise again in view of the fact that morphine, as is known, deepens the comatose state. Life prompts not to be afraid of this contradiction since temporary use of morphine to arrest convulsions helps revival of the brain eliminating exhaustion caused by convulsions. 4. Some revived patients develop hallucinations. There is an impression that they unfavourably influence further recovery of all the functions of the nervous system. Though it might seem obvious that even this chaotic activity of the brain must promote its awakening, it does not happen. Here is another contradiction. It may be explained by the fact that any load on the reviving brain, even an insignificant one, can to some measure exhaust it and thereby hinder its recovery. 5. Study of the contradictions inherent in the terminal period, that is not an exception but rather a rule at this stage of life, gives ground to make a conclusion about the presence of the leading contradiction which seems to dominate over all other contradictions observed in dying and reviving. Apparently the counteraction of dying and the factors of resistance to dying is just that leading contradiction between dying and reviving of the body which becomes the motive impulse of the whole process. For example there is a tendency for a drop in systemic arterial pressure in different types of dying at a certain stage (factor of dying). In response to this, ejection of catecholamines into the blood bed is enhanced; catecholamines acting on the heart and vessels raise arterial pressure (factor of resistance to dying). It is also known that the process of dying is characterized by the extreme tension of the brain cortex functions, and this causes its rapid exhaustion and death. However, at a definite stage of the terminal state - agony - the action of the factors of resistance to dying causes the development of protective inhibition in the cortex aimed at protecting the latter from extreme actions. Today, the rational use of modern computer technologies may considerably ease the character of resuscitator’s work. Computers may collect, keep and process the medical data, thus maximally releasing the physician’s creative potential for highly humanistic activity of treating critically ill patients. Monitor observation and computer analysis of medical data allow us to widen the possibilities of diagnosis at the patient’s bedside, to effectively correct pathological disorders, to prognosticate the course and outcome of terminal states in modern intensive case units. A computer set up in the intensive care unit must be a powerful means for advanced training of a physician; it will help to deepen knowledge of the nature of terminal states and the ways of their correction. Dealing with theoretical and clinical problems of reanimatology one should not neglect the fact that propaganda of first aid techniques of resuscitation (the simplest
195
artificial respiration, indirect cardiac massage, etc.) are substantial components of this science, for, as is generally known, even primitive methods of resuscitation timely used often solve the outcome, i.e. life or death of the patient. Nevertheless not infrequently the physician treating a lay-person cannot understand at his bedside what main causes have brought about this state of the patient and how to correct effectively those “failures” which have occurred in the dying body. This first of all testifies to the fact that the theory of reanimatology lags behind clinical practice, and many problems require a detailed study. Despite numerous investigations we do not know yet the most effective way of restoring disturbed metabolic processes in a dying and reviving body. It is necessary to find out the mechanisms of proteolytic processes mainly in the higher regions of the central nervous system in terminal states, and the methods intended for their weakening and delay. It is also necessary to find out the nature of morphological disorders especially of the most vulnerable tissues of the body in various types of dying, reversibility of these disorders and elaboration of measures promoting posthypoxic regeneration of damaged cells. Of special theoretical and practical interest is exclusive resistance of the amygdaloid complex, rather often outliving even the dying away functions of the bulbar centers in the course of clinical death. An endless number of theoretical problems arise in neurophysiology and therapy of the central nervous system affected in the course of dying of the body, i.e. what is the most favourable correlation for resuscitation between inhibition and stimulation of the central nervous system at various stages of terminal states; what is the most rational correlation of life (activity) of cortex and subcortex under these conditions; what are the most effective ways of bringing the patient out of the comatose state; what is the nature of alpha-coma; what is the cause of sudden deterioration of the successful beginning of recovery of the nervous system functions during the first days of resuscitation; what are the most effective ways of prophylaxis and therapy of encephalopathy and, finally, the most important problem: how one is supposed to achieve full-value recovery of the functions of the brain higher sections in lengthy (half an hour or longer) clinical death under the conditions of normothermia. A section of reanimatology dealing with resuscitation in mass catastrophes (disaster medicine) raises a great number of problems. They concern screening (selection of victims to be resuscitated immediately), elaboration of the simplest and most accessible techniques of resuscitation any many other items. An extremely complicated problem of working out the prophylactic measures and methods of reanimation of patient dying from AIDS should also be solved. The main conclusion of this is in the following: it is fine that the methods of resuscitation have found such a wide application in clinical practice, but the success of clinical reanimatology will depend to a greater extent on the results of a further theoretical analysis of the problems of this science. In other words, a deeper study of many unsolved theoretical problems of reanimatology should be emphasized. It is generally accepted that scientific achievement exchange is an elementary moral duty of any scientist. The Institute of General Reanimatology (earlier Laboratory) from the day of its foundation in 1936 has been keeping the closest contacts
1%
with physicians and scientists working in the field of theory and practice of reanimatology not only in this country, but also with our colleagues from many socialist and capitalist countries. It has become evident that only by joint efforts of scientists of all the World it is possible to solve such a complicated problem as struggle for life of man being in the state of agony and clinical death, i.e. to understand the transient states between life and death. It is unnecessary to say that all the participants in the symposium, results of their researches are dear to us. Perhaps I am one of the oldest researchers in the field of reanimation and it is a pleasure for me that a scientific-practical center of the type of our Instiute of Reanimatology was founded in the USA, in the country with which we are establishing more and more friendly contacts, though this center was founded 20 years later, than in our country. This center is directed by my old friend and a well-known scientist Peter Safar. We got to know each other in 1963 (later on we met many times in the USSR and in the USA, and in other countries at the Reanimation Congresses). I will not conceal that all that time I made all possible to turn him to our reanimation belief, i.e. to distract him from anesthesiological problems. I willingly acquainted P. Safar with the results of research carried out at our Laboratory, and I was glad that he took interest in that. I am happy that Professor P. Safar being much younger than me, works productively at the Resuscitation Center organized in Pittsburgh, that he will further develop the science of reanimation to which I devoted more than half a century of my life. The logics of experimental and clinical study of the problems of life and death demands making theoretical generalizations, concerning the essence of life, i.e. philosophical problems of life. Thus, the problem of life and death is one of the major problems not only of modern biology and medicine but also of philosophy. It seems expedient to touch upon one more question concerning philosophical aspects of reanimatology. I think that a closer contact between resuscitation working at the Institute of Life headed by Professor Marois in Paris studying the problem of man as a biophilosophical category, and the Institute of Man, being founded in this country by the USSR Academy of Sciences and headed by Academician I.T. Frolov, will be expedient and useful. For us this question acquires a specific significance today. Our country has entered the epoch of reforms “perestroika”, i.e. the period of progressive development, the period of qualitative changes and significant improvement in economic and all other social aspects of our life. “The main factor, - said MS. Gorbachev - that determines the essence of “perestroika” (reforms) - is to raise a man as a personality, to make a man a center of all our reforms in economics, political process and intellectual sphere”.* Life is a great gift of nature and struggle for its preservation is a noble and human duty of any physician. Control of unjustified death, i.e. dying of the still viable body in various types of pathology, especially in pediatrics, is a problem common to all
*“Pravda”, February 23, 1989, pp. l-2. and creative intelligentsia in Lvov.
M.S. Gorbachev’s meeting with representatives of scientific
197
mankind. This brings together scientists of all the world to solve this problem. This gives one a chance to be optimistic and to cherish hopes that many types of death of the present time will be reversible states in the future. Let us wish success to each other in this hard and honourable work.
Resuscifution. 19 (1990) 189-197 Elsevier Scientific Publishers Ireland Ltd.
International
Some neurological
Communication
aspects of reanimatology* V.A. Negovsky
Institute of General Reanimatology, AMS Moscow (U.S.S.R.)
Among medical sciences there has recently appeared another one, reanimatology, the science of resuscitation. This science is close to anesthesiology and to many other clinical and theoretical disciplines which to some measure have to deal with problems of dying and resuscitation of the body. The essence of this science is the study ‘of the regular patterns of dying and recovery of the vital functions of the body to provide more effective therapy of terminal states. The role of recovery of central nervous system functions in resuscitation of the body is so great that reanimatology can be called with good reason a neurological science. Therapy aimed at recovery of the brain function should be started simultaneously with measures to be taken to restore the function of the cardio-vascular system and respiration. Recovery of the body without revival of the brain should be considered as a defect of resuscitation. We consider the body revived only in case when all its functions are revived including the complete recovery of the higher brain functions. Reanimatology is closely connected with theoretical biology since it is difficult to imagine the creation of the general theory of life, the whole conception of its essence without considering the stage at which life ends. Historical data are also important in the investigation of the given problem. Study of the mechanisms of decay and recovery of the vital functions in the phylogenetic aspect, especially detection of the processes determining the more elevated resistance of some animals to the developing process of dying, is a most important route of investigation. Struggle for earlier recovery of the dying patient from a severe terminal state, especially coma, is the main aim of the successful outcome of resuscitation. Recovery of cortical regulation of physiological functions is the most effective method of maintaining the beginning revival of the body and compensation of those pathological disorders, i.e. those “failures” which had developed in the body in the process of dying and at the initial period of revival. Of course, it would be groundless to hope for the compensatory role of the higher brain functions, if blood loss was not replaced and severe metabolic disorders were not eliminated. *Address delivered by Dr. Negovsky at the International Symposium “Central Nervous System and PostResuscitation Pathology of Organism” which was held in Moscow on March 14-16, 1989. 0300-9572/90/$03.50 0 1990 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
190
Significance of compensation of somatic disorders in the reviving body for recovery of the brain is being studied in detail at our Institute. In other words, it is necessary first of all to help the brain to recover its functions, and then the nervous regulation of all the processes occurring in the reviving body will be regained. A very complicated problem of correlation of the processes of inhibition and stimulation of the central nervous system of the reviving body remains to be unsolved, and it is a subject of detailed study. The question is at what stage of resuscitation it is advisable to enhance or weaken one of the two mentioned processes to achieve a complete favourable and full recovery of brain functions. Studies into the mechanisms of genesis of hypoxic and post-hypoxic pathology of the brain have allowed us to reveal the whole complex of pathochemical factors participating in the formation of post-resuscitation encephalopathies. These include changes in the energy formation processes, disorders in protein and phospholipid metabolism, activation of proteolysis enzymes, and changes in the state of membrane systems of neurons. At present the following research is of primary importance: further study of the molecular mechanisms of neurohormonal regulation of metabolism and functional activity of the nervous tissue, investigation of the receptor apparatus connected with the effector systems of the cell, and the role of secondary mediators in the development of post-resuscitation encephalopathies. The functional potentials of the brain in the post-resuscitation period are to a considerable degree determined by a decrease in the synaptic pool, capacity for recovery of damaged islands of nerve cells, and intraneuronal contacts, and formation of the new ones. It has been established that in the early post-resuscitation period marked destructive changes in synapses are observed in the brain cortex of animals. Compensatory-adaptive processes are restricted by hypertrophy of the preserved synapses and by transformation of less mature forms into typical functionally mature contacts. Later on an intensive process of formation of new synapses takes place which promotes a more complete recovery of the integrative function of the brain. It has been established that following clinical death of various etiology and duration, activation of the protein synthetizing apparatus of neurons occurs in response to severe hypoxia. This is evidenced by an increase in the size of the nucleus and cytoplasm of neurons, increase in their dry mass and in the size of the nucleolus of neurons. The degree of this process correlates with the duration of ischemia and the extent of recovery of the neurological status of animals. These results testify to the activation of the neurons protein-synthesizing apparatus during adaptation to severe hypoxia. It has been found that during the post-resuscitation period there occur profound changes in the structural and functional state of neuron chromatin, suggesting a possible change in the spectrum of synthesizing proteins. Such a shift may be regarded as one of the factors in formation of a post-resuscitation encephalopathy. The mechanism of such change require further study in the dynamics of the postresuscitation period. Affection of the central nervous system in the post-resuscitation period is caused
191
not only by direct action of hypoxia on the brain but also by a number of extracerebra1 factors. Elimination of endogenic intoxication in the early post-resuscitation period (methods of hemoperfusion, hemodialysis, ultrafiltration, plasmapheresis, plasmametabolism, donor circulation, use of xeno-organs) produces a marked favourable effect on the recovery of the central nervous system and sometimes even determines the outcome of resuscitation. Hemofiltration has proven very effective in patients with acute renal insufficiency which developed against the background of polyorgan insufficiency and sepsis. Hemofiltration, eliminating endotoxemia and correcting metabolic disorders in case of an early and intensive therapy promotes a reversal of coma, and improves treatment outcomes. It has been shown experimentally and clinically that elimination of toxic products helps to revive the brain, and quickens its recovery from the comatose state. Let me cite an instance of our latest observations: female patient Ya., 20 years old, case history N 1353, entered the resuscitation unit of the S.P. Botkin hospital in February 1987 in an extremely severe state, stage II-III coma, which had developed as a result of severe eclampsia, complicated by acute pulmonary insufficiency. The patient remained comatose for 28 days inspite of active therapy aimed at amelioration of cerebral circulation, brain metabolism, disintoxication and antioxidant therapy. During this period of time the apallic syndrome was being formed, the intercranial hypertension was being increased. The EEG-dominant was the slow 8rhythm of 4-5 oscillations/s. The mean molecules level in plasma of blood, determined by means of spectrophotometry of acid-dissolved plasma fractions, reached 0.500 conventional units. After 3 treatments of hemoperfusion, conducted consequently during 10 days, endogeneous intoxication decreased - the mean molecules level in blood plasma decreased to 0.270 conventional units. The patient showed signs of consciousness: she opened eyes when called, carried out simple instructions, but was quickly exhausted. The EEG showed that the past of slow waves considerably decreased, single and group a-oscillations appeared. One month later after the first hemoperfusion treatment the patient sat, held her head and back; her emotional reactions were adequate to the environment. Besides disintoxication therapy producing a favourable effect on the recovery of the central nervous system, hyperbarotherapy helping to regain the functions of the reviving brain is also worth of note. Scientific workers of our Institute have revealed that even after a postresuscitation comatose state lasting 2 months, hyperbaric therapy proved capable of evoking life in the brain which seemed to be dead. Let’s illustrate this fact with clinical observations: female patient B., 64 years old, case history N 2326, entered the S.P. Botkin Hospital on the 3rd of July, 1985. She suffered clinical death due serum sickness. To the end of the second month her state was characterized as apallic syndrome, tetraparalysis, spontaneous respiration and weak swallowing functions were preserved. The EEG showed the sharply flattened curve, tending to the isoline. The computerised tomography scanning showed the signs of internal and external hydroencephalopathy. After the first hyperbaric oxygenation (HBO) treatment swallowing functions improved. The EEG of both hemispheres showed the appearance of a-oscillations. On the next day by the beginning of the second treatment the EEG curve returned to its previous form (flat line), a-
192
activity disappeared. After the second HBO treatment obvious improvement was observed, the patient fixed eyes and followed with her eyes the object showed to her. The EEG again showed a-rhythm, which was firmly registered in the following days. After the third HBO treatment the signs of consciousness were observed. Later on consciousness was restored up to the verbal contact stage. Though only chaotic restoration of the nervous system functions was observed, these observations are valid from the point of view of positive effect of the HBO in the patient with apallic syndrome, which was irreversible according to all characteristics. At our Institute the question of neurologic therapy of reanimation patients has been worked out in detail by G.V. Alekseeva and her colleagues. I will touch upon only a few general principles of therapy conducted at the clinical department of our Institute. The fact that brain restoration has become the main task of modern reanimatology does not seem to be disputable. Restoration of the cardiac activity and respiration, and normalization of metabolic function help to revive the brain and reverse damage, caused by dying. But this is not sufficient. It is necessary to think about neurologic therapy aimed at restoration, of brain function, which should be prescribed from the moment of the patient’s entrance to the intensive care unit and should be continued periodically after the patient’s discharge (rehabilitation therapy). It is pertinent to remember that already in ancient times the three gates of death were known: not only heart and lungs, but brain as well. The following caveats appear true: -
-
Use of antihypoxants and then antioxidants is useful at the very early stage of treatment. It is necessary to support a sufficient level of blood pressure, as well as to use preparations which improve microcirculation in brain vessels. These act mainly as antiagregants. Medicamental pulmonary therapy by psychostimulating means (acephen, lucidril etc.) should be conducted when contraindications are absent. General strengthening therapy and is necessary.
As far as the use of barbiturates in patients who suffered clinical death is concerned, our earlier investigations have shown that barbiturates in certain dosage and at the certain stage of reanimation only in few cases have some positive effect. As a rule, they are ineffective. The recent investigations carried out at our Laboratory (mainly as a response to some positive evaluations of barbiturates in reanimation, which appeared in literature)* showed that both in experimental and clinical study the use of barbiturates, as a rule, becomes harmful after the brain has suffered severe hypoxia, i.e. clinical death. At the same time there is no doubt that barbiturates used before clinical death may be useful. One of the specific features of the terminal period is its contradictoriness. Many processes occurring in the terminal period often differ from the processes taking *See the chapter by P. Safar “Resuscitation Safar “Brain failure and resuscitation”.
after brain ischemia” in the book by A. Grenvik and P.
193
place in the living and even sick body and look like processes contradicting our general conceptions of life. In detailed study it becomes clear that these contradictions are not errors in cognition, or contradictions from the point of view of formal logits, but they do exist in reality and reflect the essence of this period of life. A seeming contradictoriness of a number of processes observed in dying and reviving of the body not infrequently brings some researchers to a deadlock. However, even Hegel wrote in his Logics: “. . . contradiction is a root of every movement of life, only because something has a contradiction in itself, it moves, possesses an impulse to activity”. * In this connection it is proper to quote a number of statements made by V.I. Lenin in his work “On the Question of Dialectics”. “Development is the struggle” of opposites. The two basic (or two possible? or two historically observable?) conceptions of development (evolution) are: development as decrease and increase, as repetition, and development as a unity of opposites (the division of a unity into mutually exclusive opposites and their reciprocal relation). In the first conception of motion, self-movement, its driving force, its source, its motive, remains in the shade (or this source is made external-God, subject, etc.). In the second conception the chief attention is directed precisely to knowledge of the source of “self)‘-movement. The first conception is lifeless, pale and dry. The second is living. The second alone furnishes the key of the “self-movement” of everything existing; it alone furnishes the key to the “leaps”, to the “break in continuity”, to the “transformation into the oppsite”, to the destruction of the old and the emergence of the new. The unity (coincidence identiy, equal action) of opposites is conditional, temporary, transitory, relative. The struggle of mutually exclusive opposites is absolute, just as development and motion are absolute”.** Returning to the analysis of the accumulated experience the following examples of contradictions of the terminal period features can be given: 1. Practice has shown it inadvisable and even dangerous to transfer the revived patient to natural breathing. One may object to this as it contradicts the generally accepted proposition concerning the use of natural breathing as a factor stimulating the reviving cortex. At the same time this contradiction exists in reality in life. And no logical error can be found in the above mentioned assertion. Life has shown that in the given situation one should not take into consideration the generally accepted proposition on the use of stimulation of the cortex, in particular, with impulses from the respiratory center that under other conditions may be undoubtedly of use, but should conduct long-term artificial ventilation, otherwise the patient may die. 2. It is common knowledge that comatose patients are given morphine. Some researchers may be confused by the use of morphine preparations for the given category of patients, as formally it contradicts the accepted and verified proposition on the usefulness of an early recovery of the patient from coma, as it is customary to *Hegel, “Science of Logics”, Collected Works, vol. 5, p. 520. Gos. Izd. of sotsio-ekonomic literature. **V.I. Lenin, Collected Works. “Philosophical Notebooks”, vol. 38, pp. 357-361, “Progress” Publishers, Moscow, 1976.
194
consider that morphine deepens coma. At the same time the usefulness of morphine preparations in comatose post-resuscitation patients has been proved by a great number of clinical observations. This actual contradiction can be explained by the fact that with administration of morphine pain impulses stop reaching the revived brain and, thus help its recovery from coma. The action of some other factors explaining this position is not excluded, though this is a contradictory phenomenon. 3. Revived patients may develop convulsions of the cental origin. The use of morphine also proved useful in this case. However, an objection may arise again in view of the fact that morphine, as is known, deepens the comatose state. Life prompts not to be afraid of this contradiction since temporary use of morphine to arrest convulsions helps revival of the brain eliminating exhaustion caused by convulsions. 4. Some revived patients develop hallucinations. There is an impression that they unfavourably influence further recovery of all the functions of the nervous system. Though it might seem obvious that even this chaotic activity of the brain must promote its awakening, it does not happen. Here is another contradiction. It may be explained by the fact that any load on the reviving brain, even an insignificant one, can to some measure exhaust it and thereby hinder its recovery. 5. Study of the contradictions inherent in the terminal period, that is not an exception but rather a rule at this stage of life, gives ground to make a conclusion about the presence of the leading contradiction which seems to dominate over all other contradictions observed in dying and reviving. Apparently the counteraction of dying and the factors of resistance to dying is just that leading contradiction between dying and reviving of the body which becomes the motive impulse of the whole process. For example there is a tendency for a drop in systemic arterial pressure in different types of dying at a certain stage (factor of dying). In response to this, ejection of catecholamines into the blood bed is enhanced; catecholamines acting on the heart and vessels raise arterial pressure (factor of resistance to dying). It is also known that the process of dying is characterized by the extreme tension of the brain cortex functions, and this causes its rapid exhaustion and death. However, at a definite stage of the terminal state - agony - the action of the factors of resistance to dying causes the development of protective inhibition in the cortex aimed at protecting the latter from extreme actions. Today, the rational use of modern computer technologies may considerably ease the character of resuscitator’s work. Computers may collect, keep and process the medical data, thus maximally releasing the physician’s creative potential for highly humanistic activity of treating critically ill patients. Monitor observation and computer analysis of medical data allow us to widen the possibilities of diagnosis at the patient’s bedside, to effectively correct pathological disorders, to prognosticate the course and outcome of terminal states in modern intensive case units. A computer set up in the intensive care unit must be a powerful means for advanced training of a physician; it will help to deepen knowledge of the nature of terminal states and the ways of their correction. Dealing with theoretical and clinical problems of reanimatology one should not neglect the fact that propaganda of first aid techniques of resuscitation (the simplest
195
artificial respiration, indirect cardiac massage, etc.) are substantial components of this science, for, as is generally known, even primitive methods of resuscitation timely used often solve the outcome, i.e. life or death of the patient. Nevertheless not infrequently the physician treating a lay-person cannot understand at his bedside what main causes have brought about this state of the patient and how to correct effectively those “failures” which have occurred in the dying body. This first of all testifies to the fact that the theory of reanimatology lags behind clinical practice, and many problems require a detailed study. Despite numerous investigations we do not know yet the most effective way of restoring disturbed metabolic processes in a dying and reviving body. It is necessary to find out the mechanisms of proteolytic processes mainly in the higher regions of the central nervous system in terminal states, and the methods intended for their weakening and delay. It is also necessary to find out the nature of morphological disorders especially of the most vulnerable tissues of the body in various types of dying, reversibility of these disorders and elaboration of measures promoting posthypoxic regeneration of damaged cells. Of special theoretical and practical interest is exclusive resistance of the amygdaloid complex, rather often outliving even the dying away functions of the bulbar centers in the course of clinical death. An endless number of theoretical problems arise in neurophysiology and therapy of the central nervous system affected in the course of dying of the body, i.e. what is the most favourable correlation for resuscitation between inhibition and stimulation of the central nervous system at various stages of terminal states; what is the most rational correlation of life (activity) of cortex and subcortex under these conditions; what are the most effective ways of bringing the patient out of the comatose state; what is the nature of alpha-coma; what is the cause of sudden deterioration of the successful beginning of recovery of the nervous system functions during the first days of resuscitation; what are the most effective ways of prophylaxis and therapy of encephalopathy and, finally, the most important problem: how one is supposed to achieve full-value recovery of the functions of the brain higher sections in lengthy (half an hour or longer) clinical death under the conditions of normothermia. A section of reanimatology dealing with resuscitation in mass catastrophes (disaster medicine) raises a great number of problems. They concern screening (selection of victims to be resuscitated immediately), elaboration of the simplest and most accessible techniques of resuscitation any many other items. An extremely complicated problem of working out the prophylactic measures and methods of reanimation of patient dying from AIDS should also be solved. The main conclusion of this is in the following: it is fine that the methods of resuscitation have found such a wide application in clinical practice, but the success of clinical reanimatology will depend to a greater extent on the results of a further theoretical analysis of the problems of this science. In other words, a deeper study of many unsolved theoretical problems of reanimatology should be emphasized. It is generally accepted that scientific achievement exchange is an elementary moral duty of any scientist. The Institute of General Reanimatology (earlier Laboratory) from the day of its foundation in 1936 has been keeping the closest contacts
1%
with physicians and scientists working in the field of theory and practice of reanimatology not only in this country, but also with our colleagues from many socialist and capitalist countries. It has become evident that only by joint efforts of scientists of all the World it is possible to solve such a complicated problem as struggle for life of man being in the state of agony and clinical death, i.e. to understand the transient states between life and death. It is unnecessary to say that all the participants in the symposium, results of their researches are dear to us. Perhaps I am one of the oldest researchers in the field of reanimation and it is a pleasure for me that a scientific-practical center of the type of our Instiute of Reanimatology was founded in the USA, in the country with which we are establishing more and more friendly contacts, though this center was founded 20 years later, than in our country. This center is directed by my old friend and a well-known scientist Peter Safar. We got to know each other in 1963 (later on we met many times in the USSR and in the USA, and in other countries at the Reanimation Congresses). I will not conceal that all that time I made all possible to turn him to our reanimation belief, i.e. to distract him from anesthesiological problems. I willingly acquainted P. Safar with the results of research carried out at our Laboratory, and I was glad that he took interest in that. I am happy that Professor P. Safar being much younger than me, works productively at the Resuscitation Center organized in Pittsburgh, that he will further develop the science of reanimation to which I devoted more than half a century of my life. The logics of experimental and clinical study of the problems of life and death demands making theoretical generalizations, concerning the essence of life, i.e. philosophical problems of life. Thus, the problem of life and death is one of the major problems not only of modern biology and medicine but also of philosophy. It seems expedient to touch upon one more question concerning philosophical aspects of reanimatology. I think that a closer contact between resuscitation working at the Institute of Life headed by Professor Marois in Paris studying the problem of man as a biophilosophical category, and the Institute of Man, being founded in this country by the USSR Academy of Sciences and headed by Academician I.T. Frolov, will be expedient and useful. For us this question acquires a specific significance today. Our country has entered the epoch of reforms “perestroika”, i.e. the period of progressive development, the period of qualitative changes and significant improvement in economic and all other social aspects of our life. “The main factor, - said MS. Gorbachev - that determines the essence of “perestroika” (reforms) - is to raise a man as a personality, to make a man a center of all our reforms in economics, political process and intellectual sphere”.* Life is a great gift of nature and struggle for its preservation is a noble and human duty of any physician. Control of unjustified death, i.e. dying of the still viable body in various types of pathology, especially in pediatrics, is a problem common to all
*“Pravda”, February 23, 1989, pp. l-2. and creative intelligentsia in Lvov.
M.S. Gorbachev’s meeting with representatives of scientific
197
mankind. This brings together scientists of all the world to solve this problem. This gives one a chance to be optimistic and to cherish hopes that many types of death of the present time will be reversible states in the future. Let us wish success to each other in this hard and honourable work.