The neurological stage in reanimatology

RESUSClTATION

Resuscitation

29 (1995)

169-176

The neurological stage in reanimatology V. Negovsky Institute

for

General

Reanimatology,

Russian Academy

Received

Keyword:

13 May

of Medical Federation

Sciences.

1994; accepted

2.5 Petrovka

11 January

Srreer.

MOSCOW, 103c)SI,

Russtan

1995

Clinical death; Agony; Neurological state in reanimatology; Struggle of contradictions in reanimatology

1. Introduction The literature of resuscitation has repeatedly examined the first and necessary step to be taken by the practical and theoretical aspects of the science of resuscitation, namely, the investigation of cardiopulmonary resuscitation (CPR). The CPR methods introduced into medical practice have already revealed many important facts characterising the aspects of an organism recovering from clinical death. As in any other field of knowledge, there remain many tasks to be solved. For example, many CPR researchers are tempted to find means to improve coronary circulation during heart massage. One should not forget the not widely-used method of intra-arterial centripetal pumping of warm blood with adrenaline and glucose into one of the peripheral arteries, in particular the brachial artery. This method, based on the ideas of Kulyabko [l] and Andreev [2], and in combination with artificial ventilation with the help of a primitive respiratory apparatus like bellows, helped us during World War II to revive several dozens of the wounded, dying of blood loss and in a state of agony or even clinical death. This method should be regarded as an important addition to 0300-9572/95/$09.05 0 1995 Elsevier SSDI 0300-9572(94)00837-J

Science

Ireland

Ltd. All rights

heart massage. Probably, the combination of heart massage with cardiopulmonary bypass used for many years in experiments by Russian scientists [3-41 would be more productive. However, shortage of time, unfortunately, makes it impossible for resuscitators to use this method widely. It can be used only in rare, very favourable cases. There are problems in the CPR aspects of respiration and its restoration, but we must concentrate on the new task facing the scientists of resuscitation - the central task of studying neurologic aspects of resuscitation. It has become evident that the non-revival of the higher brain sections makes resuscitation meaningless during CPR. It has become most important to revive the cortex to consciousness. Thus, the new step in CPR is to focus all resuscitation studies on neurologic aspects. 2. Clinical and bi&qgical death Clinical experience confirms the fact that the time taken for clinical death to occur does not exceed 5-6 min in adults and 7-8 min in children. At low temperatures, these times may be extended a little. Information in the literature concerning the complete revival in ordinary temperature conreserved

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ditions, after 20~30 min clinical death, cannot be considered proven. It only disorientates the doctors and does harm to the development of clinical resuscitation. 3. Clinical death and hypothermia During hypothermia, the period of clinical death is known to be longer than under usual temperature conditions. Positive results of reviving animals after 2 h clinical death in hypothermia were obtained in our institute. It is worth pointing out that death of these animals occurred under low body temperature (about 16 or 20°C). Certainly, it is necessary to obtain positive results of revival with the animal’s body temperature decrease having taken place after the occurrence of clinical death. This is a more difficult, but by far a more important task. It is common knowledge that people drowned in cold water are easier to revive than those drowned in warm water. This progressive and useful idea for resuscitation is however far from being widely used in practice. This is a beautiful, but real dream, though its realization demands much effort. The use of low temperatures to preserve the brain from severe damage caused by hypoxia is a complicated but promising task. Its realization will demand a more adequate narcosis combined with hypothermia. The set of problems concerning the use of hypothermia in resuscitation (including the postresuscitation restoration period) is one of the most topical tasks of resuscitation. 4. Some neurologic issues of resuscitation There is no doubt that measures aimed at the restoration of the central nervous system (CNS) are the most important. Naturally, it is necessary to revive and normalize the functions of the cardiovascular system, respiration, metabolism and at the same time to use all available means to restore the CNS functions. It does not mean, however, that the reviving process can exclude other pressing questions. For example, in the case of massive blood loss it is urgent to compensate this immediately; in the case of trauma, to render emergency trauma-

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tological aid and so on. However, the necessity of complete restoration of the cortex can be considered as essential. Adequate and timely methods of resuscitation should be performed as well as in other types of therapy. All the above mentioned facts suggest that resuscitation should be looked upon as a neurologic science, and this idea should be our scientific motto. It is expedient to use medications improving cerebral circulation and promoting the access of blood to the reviving brain e.g. certain stimulants or, more often, drugs to decrease the brain’s activity, or opiates and other means of promoting the patient’s revival. Even present-day medical techniques do not exclude methods of psychological influence affecting psychic states and resistance to pathological process and making the patient believe (sometimes without any grounds) that he will recover and live on. Emmanual Kant stressed the positive role of the will in overcoming pathological .processes [5]. Often 3 or sometimes 6 months after being discharged from the resuscitation unit, the patient develops various psychoneurologic disturbances demanding therapy. This is an important aspect of modern resuscitation. It is possible to decrease the occurrence and severity of disturbances and to speed up the process of psychoneurologic stabilization and social adaptation Rehabilitation units for resuscitated patients are not as necessary as for patients with myocardial infarction. Only patients with an obvious prospect of restoring the disturbed CNS functions should be sent to such units. Otherwise, they will be full of patients who can recover only primitive elementary functions of the higher CNS sections due to irreversible cortex damage in spite of prolonged and persistent treatment. Such patients should be sent to chronic neurologic units or specialized sanatoria. Any resuscitator knows the importance of timely and correct artificial respiration. That is why it is important to understand that the late start and early (untimely) withdrawal of artificial ventilation, which leads to severe irreversible neurologic disturbances, is often the most common mistake in resuscitation. It has been established that patients who have survived a terminal state, especially those who were unconscious, need prolonged

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artificial ventilation. Using the data of the electroencephalogram and the clinical picture, one can predict, whether the discontinuation of artificial ventilation at that time will be favourable or not. 5. Hyperhohrapy

(hyperbaric oxygenation)

The use of hyperbarotherapy in resuscitation is just starting. At the same time some experience, acquired in our institute, makes it possible to conclude that hyperbarotherapy is an important and necessary element in a complex of measures preventing and treating encephalopathies in revived patients. A young scientist of our institute, AV Bukreev, has been researching into this problem for the last 2 years. Patients (n = 72) with posthypoxic encephalopathy have been observed. The duration and frequency of hyperbarotherapeutic sessions have been determined by the nature and severity of neurologic disturbance. It has been shown that hyperbaric oxygenation considerably improves the outcome of neurologic rehabilitation, shortens the term of the patient’s stay in the hospital and improves the quality of life. The pressure in the hyperbaric cell was chosen individually in the range from 1.4 to 2 atm. The degree of structural - morphological changes was determined with the help of computer tomography. In spite of the fact that some patients had destructive damage, leading to hydrocephalus, atrophy and clinical regression of other complications, neurologic symptoms was obvious. A high level of rehabilitation was achieved. Of 18 patients, unconscious after resuscitation and treated with prolonged hyperbarotherapy, 9 achieved restoration of consciousness and could perform simple jobs. The report on the use of hyperbarooxygenation in resuscitation was made by me at the Intemational Conference on Hyperbaric Oxygenation in Padova in 1989, organized by the Department of Anaesthesiology and Intensive Therapy (Director, Prof. D. Giron) of Padova University in collaboration with a skin-divers’ club. 6. Addithnl

therapeutic measures

The use of these techniques also helps to restore the CNS functions to the whole reviving organism. 1. Haemosorption to counteract endogenous in-

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toxication, usually developing in these patients and impeding the process of revival. 2. Hemotiltration which is a conventional method of blood purification, based on ultrafiltration of large volumes of liquid. 3. Prevention of hypercoagulation to prevent the occurrence of shock in organs or hypocoagulation (most often occurring in obstetricgynaecological practice). 4. Prevention of hyper-osmolarity syndrome when blood plasma osmolarity increases to 340 mosm/l and leads to the loss of liquid accompanying severe neurologic disturbances. Hypo-osmolarity syndrome when blood plasma osmolarity decreases to 280 mosm/l leading to brain edema should also be prevented. 5. Intravascular systematic laser irradiation of blood [7] is carried out after the introduction of a lightguide through a subclavian vein catheter into the superior vena cava. The power of radiation on the lightguide end is 20 mW, duration over 30 min. Three sessions of low intensity He-Ne irradiation are used. The method is used as a part of other resuscitation measures and makes it possible to improve the functions of blood transportation. decreases peripheral resistance, ameliorates the circulation and reduces peroxide oxidation of lipids. A number of other methods are used less often. But, according to published data, these can also improve and accelerate the restoration of vital CNS functions: 6. Ultraviolet blood irradiation. 7. Magnetic blood processing. 8. Blood oxygenation using ozone (91. 7. Stimalrthg

the restoration of eorticrtl fkmctions

The studies of the latest decades have cotirmed the idea that restoration of higher brain sections’ functions helps to revive all the functions of the organism. It fully corresponds to IP Pavlov’s concept. The terminal state should not be considered only as hypoxia. Another important factor is added, namely, the brain’s struggle for life. The damaged brain has to carry out a tremendous job which exhausts it. Any pathological process occur-

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ring in a reviving organism can impede the processesof revival or even stop them. The question of balance between suppression and excitation in the CNS during terminal states as well as in the CNS pathophysiology in general, is one of the most important and complicated. A resuscitator is often tempted to accelerate restoration of the cortex, to bring into action the cortical regulation of physiological functions as the most powerful and often decisive one for the outcome. But the untimely, premature restoration of the cortex can exhaust it [lo]. The vulnerable cortex of the reviving patient must be treated very carefully. Thus, routine advice in resuscitation units is: ‘Don’t bring the patient into consciousness too fast.’ Rest, sometimes with narcosis or drug-induced sleep can be more effective than premature awakening. An attempt to start a conversation with a survivor after a terminal state, or even simple questions exhaust him quickly and he stops answering them. There is one more index of an early restoration of cortical functions. The analysis of electroencephalograms as well as the clinical picture can help answer the question whether the cortex activity was started in time or prematurely? The electroencephalographic research was conducted in our institute by Prof. AM Gurvitch, and similar research in Germany by Prof. Hossmann. 8. Use of barbiturates and morphine in resuscitation

but morphine should be used to create protective inhibition (1987). Morphine is close to endogenous opiates, encephalins and endorphins. The importance in regulating physiological functions has been well established. Maisky et al. [8] wrote about this and about its role in treating terminal states. Endorphins and encephalins raise the vital activity of the organism and moderately supress it. Barbiturates have only one effect. They act to supress the vital activity of the organism. Our data fully confirm this point (Negovsky VA, Alekseeva GV). Morphine has been used intravenously in doses inducing the registration of &rhythm on the electroencephalogram (4-7 OS&). The dose was usually 2-4 and in rare cases up to 6-8 ml of 1% morphine solution/day. When the patients in the resuscitation unit had disturbed consciousness, the electroencephalogram registered slow oscillations. The use of morphine removed &waves (l-3 OS&) and stabilized the rhythm in the range of 4-7 OS&. Though these patients were ‘somnolent’, they could be woken and verbally contacted. When the patients were disoriented and the electroencephalogram registered mainly &oscillations (15-25 OS&) the use of morphine also stabilized 8oscillations, and then induced o-rhythm. Alongside this, psychic disturbances disappeared. There is reason to suppose that morphine will be used more widely in resuscitation units to treat patients after terminal states, especially after coma

Ull. There is no doubt that analgesic drugs must be used when patients suffer from acute pain. A dying patient aware of his hopeless state is often hyperexcited and the doctor usually uses medicine making the patient more quiet and alleviating his psychic state. Probably, it is more correct to speak about medicinal sleep, especially for children in terminal states. Using pain-easing drugs and studying their effect on the dying and reviving organism, we spent much time on barbiturates (1952- 1959 and again in 1983 after Prof. P Safar’s articles published in the 1970s and assessing the positive effects of barbiturates in resuscitation). Unfortunately, our erroneous steps were repeated by researchers in other countries. Only recently we have come to the conclusion that not barbiturates

9. The use of analgesics in unconscious patients Clinical observations have shown that the loss of consciousness in resuscitated patients does not exclude the necessity to use general or local anaesthesia. Pain impulses from peripheral parts of the body go along spino-thalamic tracts to the thalamus as the main sensitivity collector. They can harm or even damage the brain irreversibly, when the cortex does not yet feel the pain and can not help the organism to react to it adequately. Our experience of treating the wounded at the front during World War II confirmed our supposition about the necessity of using anaesthesia in reviving wounded unconscious patients. I

V. NegovskyI Resuscitation 29 ( 1995) 169-116

remember one very demonstrative observation. A wounded man with severe damage to his right foot was admitted to the medical batallion tent. Amputation was necessary. During the preparation for the operation, clinical death occurred. The resuscitation measures were fruitful: the cardiac activity was restored, weak respiratory movement and Iirst signs of cornea1 reflexes resumed. At that moment, the chief surgeon of the medical batallion came and announced indignantly to the physicians on duty: ‘Why are you losing time? The patient is unconscious, you must take the advantage of the situation and amputate his damaged foot.’ Under military conditions, this command was not to be disputed. The operation was performed and brought sorrowful results. The revived heart quickly died, as well as weak respiratory movements and cornea1 reflexes. Within several minutes, all the signs of revival disappeared. Clinical death recurred, which was fatal for the patient. The issue of obligatory use of local anaesthesia in resuscitation patients without consciousness is sufficiently grounded. Further research into modern multi-component balanced anaesthesia must prompt the possible use of this kind of pain relief in resuscitated patients [12]. 10. Resuscitatedpeople’sperception of dying

It is unnecessary to deal with the statement that some resuscitated people’s words about what they saw or heard during clinical death are not proof of life after death. They only demonstrate the fact that a resuscitated patient can remember the perverted impressions which he could have during dying or in the beginning of revival. Thus we can speak about the production of a dying, functionally disintegrating or reviving human brain. The majority of people who survive clinical death, say that they were just asleep, i.e. they speak about the clinical death as about a short sleep. I remember a g-year old girl who underwent clinical death as a result of asphyxia following spasmodic croup, who said afterwards: ‘How well I have dozed.’ It was her first sentence when she was revived. Let me describe one more clinical observation which we had during World War II in the bat-

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tlefield hospital, which was situated 7-8 km from the front. We had a soldier with a severe leg wound and massive bleeding. While his wound was being treated, he developed clinical death. Artificial respiration with the help of a primitive bellows-like apparatus and primitive intubation was started immediately. Revival of the heart was carried out by intra-arterial centripetal (to the heart) pumping of warm blood with adrenaline and glucose via the left brachial artery. The patient was revived. For one day he was in a state near to sleeping, then gradual awakening and restoration of consciousness began. It was one of our first cases of resuscitating people in military conditions [3,13,14]. It aroused great interest not only among physicians, but among military journahsts as well. When the wounded man was asked by one of them: ‘Tell us, what you saw in the other world’, he answered: ‘I slept through my death’, It is worthy to note that similar answers can be heard from many people who were revived after clinical death. Thus, this observation adequately reflects the processes taking place during revival. Diffuse inhibition developing in the cortex during dying and deepening during clinical death, naturally, excludes a possibility of feeling any irritation of the cortex. When the patient started to revive under resuscitative measures he could not speak about the things which had taken place during clinical death, because he had not lived then, he had felt nothing. His brain had stopped functioning as a whole, though some minimal dyingaway metabolic processes in individual cells could continue for a while. This state is not identical to the notion of ‘brain death’, when resuscitation can be legally withdrawn if brain death is confirmed according to established international rules, as the dead cortex can not revive. 11. The struggle of contradictions as the motive force of tbe processof dying and reviviq

Discussing theoretical aspects of the science of resuscitation, it is necessary to speak in short about a philosophical problem concerning the contradictions which are the motive foree of any process, here - of the process of dying and reviv-

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al. Hegel discovered a principle of self-movement as a result of the struggle of contradictions, studying this phenomenon on the basis of the development of the absolute idea [ 151. The representatives of materialistic philosophical trend applied these statements to everyday life. We think that this general philosophic conclusion should be applied to the problems of resuscitation. The processes of dying and revival as well as other processes of life activity develop by arising the contradictions. Thus, it is found that in different types of dying, during certain stages, a tendency of decreasing systemic arterial pressure appears (factors of dying). As a response, catecholamines are ejected into the blood in bigger quantities which affect heart and vessels to increase arterial pressure (factors of resistance to dying). The processes of excitation in the CNS can alternate with the processes of inhibition, and during a certain stage one will predominate. Processes of hypocoagulation can appear on the background of hypercoagulation, hypotension on the background of hypertension. The phenomenon which takes the leading place in the life activity or is supported by therapeutic measures, will give a positive or negative result. Thus, we can speak about the clash of 2 processes in critical states, (i) maintaining and developing life activity and, to the contrary, (ii) worsening the vital processes or even suppressing them (independently or in combination with other factors) and leading the organism to death. In other words, the struggle of the factors of dying and factors of resistance to dying (these factors concern the real pathophysiological processes) is the main motive contradiction, determining the development of dying and revival [16]. 12. Immunity

Until recently it was thought that any severe conditions were accompanied by deep changes in the immune status, which was interpreted as the secondary immune deficit. The development of the endogenous intoxication syndrome and purulentseptic complications in such patients confirms this interpretation. But research carried out by Prof.

VN Semenov, Director of our institute and his colleagues (OP Vrublevsky, VV Yerofeev et al.) gave reason to revise it. It was shown that many patients at a certain stage after resuscitation have depression of one link of immunity (for example, cellular), which may combine with activation of another link (for example, humoral) and vice versa. Immune reactions should not be considered protective. They can produce toxic substances, such as interleukin-I (IL-l) and tumour necrosis factor (TNF, cachectin). The quantity of the latter in patients after terminal states of any genesis exceeds the norm many times, and quickly (within l-2 days) leads to a considerable loss of weight which serves a clinical demonstration of this phenomenon. Activation and even hyperactivation of the immune system or its separate links can last indefinitely long, but it can also be replaced by its disintegration and then insufficiency, known as secondary immune insufficiency. The development of immune tolerance as a response to the appearance of numerous antibodies and antibacterial antigens (immune distress syndrome) is also possible. The following practical conclusion was made the monitoring of the revived patient’s immune reaction must be done in accordance with the outcome of resuscitation. Immuno- depressants or immunostimulators must be used. If such monitoring is possible, preference must be given either to immunostimulators or immunodepressants. Hypoxic and post- hypoxic CNS damage, manifesting as brain death, apallic syndrome, vegetative state and others, play a certain role in the pathogenesis and desintegration of the immune system. The difficulties of explaining sudden changes of the variants of immune disturbances are always connected with the changes in the clinical picture of a main disease. Such changes are characteristic of patients whose central regulation of physiologic functions was practically stopped or considerably damaged. According to Prof. VN Semenov, immune reactions seem to be beyond the control of the exhausted and damaged CNS. It is obvious that all these disturbances in the immune system make restoration of the CNS functions more complicated during resuscitation.

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13. Conclu~ The science of revival was bound to appear from the logical and historical point of view, and it did. To my mind, its appearance became one of the most important events of the natural sciences of our time. We entered the phase of studying the last stage of life and, if possible, its reversibility, i.e. the revival of a dying man in an agonal state or even clinical death [ 181. At this stage, some characteristic features of complicated interactions between physiological functions can appear, which cannot always be found in the conditions of normal functioning of the organism, and which manifest themselves more clearly on the final stage of life. It is another condition of studying the mechanism of dying and restoring the physiological functions. I note with gratitude and respect the words of support and approval of my investigations by the then U.S. Vice-president Hubert H. Humphrey who visited and acquainted himself with our institution in 1962 and also the eminent American scientist Prof. Claude S. Beck [19]. In this article I mentioned some trends of research, carried out in our institute. In this connection I remember with gratitude the published work ‘Cardiac Arrest and Resuscitation’ by Prof. HE Stephenson (Columbia, Missouri, USA, published in 5 editions). This was and remains a very useful book, especially in the course of founding our institute. Naturally, I must express my respect for the studies by Prof P Safar, who has been leading the International Resuscitation Research Center of the University of Pittsburgh, USA, which he founded and which is similar to the Institute of Reanimatology in Moscow which was first organised as a laboratory in 1936 [20]. I am happy that the studies of the processes of dying and resuscitation, started in our institute in the 1940s with the aim of finding out the ‘mysteries’ of life and death and the methods of revival, are being carried out in various countries of the world. There are still many problems in resuscitation as well as in other fields of scientific knowledge which are to be solved in the course of its further development. The restoration of the central regu-

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lation of physiological functions is one of the fundamental tasks of this science. In this respect we can define death as a loss of the cortical regulation of these functions. Life as a biosocial being is impossible without a revived cortex and subcortex. I do not touch upon the so-called vegetative life, when the revived patient develops brain death or the irreversible damage of big parts of the higher brain sections [6]. There are reasons to suppose that further research in the field of resuscitation will give new, more effective methods of revival, including the full restoration of CNS functions. It gives first of all an opportunity to save many hundreds of people from death, from those types of dying, when the attempts to resuscitate -- on the level of knowledge of the end of the XXth century - are unsuccessful. Let me conclude by describing one archaeological discovery which directly refers to our speciality. In the middle of the last century, scientists found a wonderful example of ancient Greek art - the altar of Zeus in Pergamon and the remnants of the library and ancient hospital. A motto could be seen on the facade of the building: ‘No entrance to death’. The words of ancient Greece coincide with the ideas of modem resuscitation. It would be fine to see this wonderful motto, this dream or belief in human power, on the facades of modern hospitals. References 111 Kulyabko AA. Experience of reviving the heart. Rev Russian Acad Sci 1902; 16(5): 175. Further experience of reviving the heart, I: 189. PI Andreev FA. Experience of reviving cardiac activity, respiration and the central nervous system functions. Issues Sci Med 1913; 2: 137-170. 131 Bruhonenko SS. Use of artificial circulation method for resuscitation. In: Bruhonenko SS (ed), Works of the Scientific Research Institute (SRI) of Experimental Physiology and Therapy, vol. I. SRIEPT Biomedgiz, M. 1937; 6-22. 141 Bryukhonenko SS, Chechulin SI. An experience of Isolation of a Dog’s Heart with Demonstration of the Apparatus. Leningrad: Trudy II Vsesoyuszn. S’esda Fisiol, 1926; 289-290. 151 Kant E. Tracts and Ictters.(About the possibility of the soul overcoming painful feelings with only the help of the will). Science M. 1980.

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[6] Alekseeva GV. Clinical Neurology of Terminal States. In: Modem Problems and Prospects of Development of Modem Reanimatology. M. 1994, p. S-10. [7] Avrutzkiy MYa. Influence of low intensity laser radiation on major biological processes and homeostasis of patients. J. Anaesthesiol. Reanimatol. 1991; N.5: 74-79. [8] Maisky AI, Vedenikov MN, Lakin BA, Chistaykov VA. Biological aspects of narcomania. Medicine M. 1989. [9] Negovsky VA, Gurvitch AM, Zolotokrylina ES. Postresuscitation diseases. 2nd edn. Medicine M. 1987; 382. [IO] Negovsky VA, Alekseeva GV. Prevenzione e terapia degli stati di coma nei patienti sottoposti a rianimazione Atti del II Congress0 Intemazionale, Milano, Sola Provincia, 24-26 June, 1986. [II] Negovsky VA. The use of morphine to prevent postreanimation encephalopathy. Adv Pain Res Therap 1990; 14: 363-366. 1121 Shifrin GA. The concept of antinociceptive anaesthesia. J. Anaesthesioi. Reanimatol. 1993; N.4: 69. [13] Negovsky VA. Agonal states and clinical death: Problems in revival of organism. M. 1943; 170.

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[14] Negovsky VA. Therapy of agonal states and clinical death in an army region. M. Medgiz. 1945; 94. [15] Hegel. Science of logic M.O. 1937, vol. 5, 715. [16] Negovsky VA. Some methodological problems of modem reanimatology. Voprosy Philosophii 1978; 8; 64-73. [17] Vrublevsky OP, Erofeev VV, Polikarpova SV. et al. Computer consultive system for promoting rational antibacterial thereapy to increse detoxication efficacy. In: Terminal states and the post-resuscitation pathology of organisms: pathophysiology, clinic, prevention and treatment. M. 1992, p. 111-122. [18] Negovsky VA. Essays on reanimatology. Medizina M., 1986, 256~ (published in English Mir Publisher 1989, 279). [19] United States Senate International Health Study Congressional Record, October 25, 1962. [20] Safar P., Bircher NG. Cardiopulmonary-cerebral resuscitation, 3rd edn. London: W.B. Saunders, 1988.