The detailed investigation of the extreme states of life over recent decades has made it possible to single out especially the problem of the final stage of terminal states, the stage of clinical death. We hardly need to explain how important it is for the theory and practice of reanimatology, since the concept of ‘clinical death’ has become a most essential one in the science of the dying and restoration of vital functions.
Definition of the concept of clinical death has marked a new level in our knowledge of the phenomenon of death. It has been shown that there is a transitory state between life and death, that is not yet death but can no longer be called life.
Clinical death is an example of the unity of discontinuity and continuity. From the moment of its approach, life, in the common understanding of the word, is no more, but at the same time those elements of life that mark the lasting continuity of vital processes are still present, and make resuscitation of the organism possible during this period.
Recognition of this situation has completely refuted the old notion that death sets in directly cardiac activity and respiration cease. At the same time it has confirmed the possibility of active struggle with death and of full restoration of the organism’s fading functions by the application of the appropriate reanimation measures.
Clinical death must therefore be considered a reversible stage of dying, a transition from life to so-called true biological death, i.e. to the period when processes of disintegration begin within the various organs and tissues and resuscitation of the organism as an integral system is no longer possible.
The setting in of clinical death is preceded by a pre-agonal state and by agony. In the first stage of dying, in other words throughout the pre-agonal period, disorders of haemodynamic and respiration predominate, causing the development of hypoxia and tissue acidosis. The functional impairment of a number of organs and systems that develops on this background aggravates the disturbance of circulation and fosters a transition to the next stage of dying.
It must be stressed that the determining factor during the preagonal state is the type of metabolism; at this time the organism continues to obtain its energy supply basically from reactions that still occur with utilization of oxygen.
The duration of the pre-agonal period varies considerably, and depends on the main pathological process, and also on the character of the adaptive compensatory mechanisms. Thus, in the case of sudden cardiac arrest caused by ventricular fibrillation there is virtually no pre-agonal period. On the contrary, during dying from loss of blood and in traumatic shock, progressing respiratory insufficiency of various aetiologies and a number of other pathological states it often lasts for many hours.
The transitional stage between the pre-agonal state and agony is known as the terminal pause. It is particularly clearly expressed in dying from loss of blood and has been quite fully studied experimentally. The terminal pause is characterized by respiration suddenly ceasing after sudden tachypnoea.
At this point the bioelectric activity of the brain disappears and the corneal reflexes fade. On the ECG there is usually a replacement of nomotopic rhythm by infrequent ectopic impulses. Oxidative processes are repressed and glycolytic processes increase. The duration of the terminal pause varies from five or ten seconds to three or four minutes.
Agony begins after the terminal pause; this is a complex of the last manifestations of the organism’s reactive and adaptive functions directly preceding death. The most important feature characterizing the state of the central nervous system during the agonal period is cutting out of the functions of the higher sectors of the brain, especially of the cortex.
The bulbar centres, once relieved of the regulatory influence of the cerebral cortex begin to ‘organize’ as it were one more, last attempt in the dying organism’s struggle for life, which puts a stamp on the whole of its vital activity, giving it a chaotic and primitive character. One of the manifestations of agony is often a temporary increase in the almost extinct processes of respiration and circulation, sometimes accompanied by a short-term regaining of consciousness. In this period decerebrate rigidity and general tonic spasms are often observed.
The main energy background on which the organism’s vital activity depends during agony is glycolysis, which in turn leads to rapid accumulation of incompletely oxidized metabolic products: viz. lactic, pyruvic, aceto-acetic and other organic acids. It can be supposed that, due to depression of the oxidative enzymes, what oxygen is left in the brain’s vessels is no longer utilized at this stage of dying. This applies most of all to the higher sectors of the central nervous system, and least of all to muscular tissue.
The first inhalation acts as a sign of the beginning of agony after the terminal pause. Respiration is at first weak, then considerably increases, and after reaching a given maximum, gradually weakens and ceases. Agonal respiration differs sharply from normal: involvement of all the respiratory muscles, including the accessory ones is highly typical of the act of inhalation.
The research carried out allows us to suppose that the supplementary spinal centres are also involved in performance of the agonal respiratory act.
In addition to the appearance of agonal inhalation, one notes an increase in the frequency of cardiac contractions, and a certain increase in blood pressure, which, naturally, cannot ensure full vital activity of the higher sections of the brain. A short-term restoration of sinusal automaticity may be observed on the ECG, and of auriculo-ventricular conduction, which quite frequently develops in the period preceding agony. Widening of the coronary vessels and arteries carrying blood to the brain and vasospasm of the internal organs are observed during agony, which can serve as an example of the peculiar compensatory reaction of the organism to extreme influences.
Temporary renewal of relatively effective cardiac activity and respiration creates favourable conditions for the restoration of the cerebral cortex’s bioelectric activity, of pupillary and corneal reflexes and occasionally of consciousness. In the absence of energetic curative measures, however, this spark of vital activity is the last. How expressed it is depends on the concrete pathological background. Then cardiac activity and respiration cease and clinical death sets in.
During the first two minutes of clinical death, a drop in sugar and glycogen content can be observed in brain tissue as a result of glycolysis. Exhaustion of carbohydrate reserves and accumulation of lactic acid occur in both the cortex and the white matter of the brain and in the medulla oblongata.
At the same time the content of macro-ergic phosphorous compounds drops. The total of ATP and ADP is reduced by about half in the first three minutes of clinical death, and then gradually drops, not reaching zero, however, even during the next 20 minutes. Phosphocreatine disappears very quickly from brain tissue; after five minutes of clinical death not even traces of it can be found.
Thus, during the first five or six minutes of clinical death the content of carbohydrates and macro-ergic compounds in brain tissue drops to such an extent that there is a sharp reduction in the processes of glycolysis, and further splitting of phospho-carbohydrate compounds takes place very slowly. But the brain tissue receives sufficient energy to maintain the structure and viability of the great majority of nerve cells for five or six minutes.
The setting in of clinical death is characterized by a number of clinical signs. Externally the person’s body has the appearance of a corpse: consciousness, respiration, and circulation are absent; full areflexia has set in; the pupils are expanded to the maximum. The organism as a whole no longer lives. At the same time one can observe isolated carrying on of particular vital functions in individual tissues or organs sharply reduced and no longer subordinated to central nervous and humoral influences.
The extinction of metabolic processes takes place in a certain order. The oxygen content of arterial blood gradually decreases after cardiac arrest and there is an accumulation of incompletely oxidized metabolic products; the pH of the blood drops.
The heart persistently retains its functions of automaticity and conduction after cessation of its mechanical work. These functions are clearly manifested in the form of gradually weakening bioelectric activity of the heart not infrequently for 20 to 30 minutes after the setting in of clinical death. Gord is right that the phonocardiogram can signal the onset of clinical death much earlier than the ECG.
The bioelectric activity itself, and the degree to which it is affected by the extracardiac innervation preserved in the early stages of clinical death, depend to a considerable degree on how long dying takes. Conditions are most favourable for them when clinical death sets in after a short period of dying. Then consecutive changes are noted on the ECG during clinical death and several phasic changes connected with the periodic predominance of the effect of the sympathetic or parasympathetic sector of the vegetative nervous system on the heart.
Observations on dogs that have died from acute haemorrhage have shown that stimulation of the heart continues at a relatively high rate — 45 to 60 beats per minute — immediately after the setting in of clinical death. As will be shown later, the form of the ventricular complex on the ECG can be very close to normal at this time, sometimes giving an impression of adequate cardiac activity.
The effect of hypoxia is reflected to a great extent on the conduction functions between the two sectors of the heart. As a result of a sharp lengthening of the P-Q interval on the ECG, the R wave proves to be closer to the T wave than to the auricular P wave. In experimental conditions this change in the form of the ECG is a characteristic sign of the onset of clinical death. After a minute to a minute and a half the rhythm of the heart decreases, then incomplete and complete auriculo-ventricular block develops, after which the slower activity of the lower-laying foci of cardiac automaticity of nodal or idioventricular origin is observed.
Usually, however, auriculo-ventricular conductivity is restored after a minute or two and the sinus node of automaticity once again becomes the pacemaker. This change of pacemaker is sometimes repeated two or three times. The periodicity of this process is already detectable during dying through the effect of an alternate increase and decrease in the tonus of the parasympathetic nervous system.
Five or six minutes after the setting in of clinical death there is a more profound disturbance of intraventricular conductivity. The ventricular complexes lose their specific character and take on the form of diphasic and then monophasic deviations, the amplitude of which gradually decreases. Sometimes widely spaced low-amplitude ventricular complexes can be observed for 15 to 30 minutes after clinical death. The bioelectric activity of the heart occasionally terminates by fibrillary oscillations.
The phasic character of the changes on the ECG during the first minutes of clinical death, mentioned above, is particularly marked after a short period of dying, i. e. in the conditions most favourable for the conserving the functions of the centres of the vegetative nervous system. On the contrary, after more protracted dying, when deep narcosis has been used, or in atropine poisoning, these changes do not take place and rhythm simply decreases gradually in frequency during the development of clinical death. All this indicates that the periodic changes of cardiac rhythm during clinical death are related to the periodicity of the still functioning extracardiac innervation, as is also the case during dying.
The conservation of neuroreflex influences on the heart during clinical death is confirmed by other facts. One of these is the regular disruption of cardiac rhythm due to irritation of the mucous membrane of the trachea during intubation. With more painful irritation of the sciatic nerve there is an even more noticeable disruption of rhythm, even to the development of fibrillary oscillations. The consecutive changes in the form of the heart’s bioelectric activity during clinical death depend on the severity of the hypoxia. They can in turn serve as an indication of the degree of cardiac hypoxia.
From the moment of the setting in of clinical death, after the disappearance of visible signs of external respiration there are bursts of oscillations of biocurrents in the reticular formation of the medulla oblongata, which are the sole confirmation that its activity as the respiratory centre has been preserved. Ionic activity in the respiratory and certain other skeletal muscles is recorded at this time on the electromyogram, which is evidence of continuing stimulation of the motor neurons of the spinal cord.
In the first minutes of clinical death, the beginning of which is conventionally taken as the last agonal inhalation or the last cardiac contraction, some reflex reactions of the organism to external stimulation are also preserved. During intubation, for example, extinct respiration may be restored. This reflex is associated with stimulation of the receptors of the superior laryngeal nerve, the nucleus of which is located in the medulla oblongata near the respiratory centre.
During dying and the beginning of clinical death protective inhibition apparently develops in the central nervous system as a result of inadequate nutrition of the nerve cells and their intoxication by the products of disturbed metabolism. This inhibition arises first in the higher, more subtly organized levels of the central nervous system, responsible for psychic functions, and afterwards in the subcortical and stem regions, which lose their regulatory functions over vegetative intraorganic processes. At this time oscillations of biocurrents are already not observed on the ECoG. Later a temporary total arrest of the vital activity of the central nervous system sets in.
The duration of clinical death depends on the length of time the cerebral cortex survives in the absence of circulation and respiration. Signs of the alteration of cells begin the moment clinical death sets in, and the longer that takes, the greater are the disorders. But even after five or six minutes of clinical death the damage to a considerable part of the cortex’s structural elements is still reversible, which makes full resuscitation of the organism possible. This is due to the high plasticity of the central nervous system, which enables the functions of the destroyed cells to be taken over by others that have preserved their vital activity.
The duration of clinical death depends in each case on several causes. Animals that have a less subtle and complex organization of the central nervous system in the functional and morphological senses can survive lengthier periods of clinical death than humans; and cold-blooded animals survive longer periods of circulatory and respiratory arrest than warm-blooded ones.
In normal temperature conditions the period of clinical death in humans does not, as a rule, exceed three to six minutes. The character and length of the preceding period of dying also have considerable effect on the duration of clinical death. With unprotracted dying, the period of clinical death is usually lengthened. In those cases, however, where dying is rapid but the process is tempestuous, accompanied with sharp stimulation and chaotic loss of strength, the period of clinical death is shortened.
When such phenomena are encountered in conditions of lengthy dying the period of clinical death shortens even more. Thus, for example, when the organism spends a long time during dying in conditions of severe hypotension, resuscitation becomes impossible even a few seconds after the cessation of cardiac activity because of exhaustion of all energy resources and of severe morphological damage. In such cases it can be conventionally said that the organism died even before cardiac activity and respiration ceased.
The different periods of clinical death in rapid and protracted dying can be explained by the peculiarities of the switching on of the compensatory mechanisms. In lengthy dying, for example after prolonged haemorrhage, when the damaging factor has a gradual effect on the organism before profound hypotension sets in, the compensatory mechanisms are already in conflict with the damaging factors. In particular there may be an improvement of the blood supply to the brain owing to circulatory changes leading to an increase of blood flow in the brain’s vascular system and a decrease in other organs.
In this case consciousness and the electrical activity of the higher sectors of the central nervous system last for a comparatively long time, whereas considerable changes take place in the other organs and tissues. When, over a lengthy period, it has not been possible to eliminate the cause producing the terminal state, degenerative, even necrotic, changes develop in the liver, kidneys, and myocardium, whereas the changes in the higher sectors of the brain are much weaker.
The picture is quite different with rapid dying. The compensatory mechanisms do not have time to come into the struggle for the organism’s life and are therefore conserved. And because of the shortness of the period, severe disorders do not have time to develop within the tissues, and clinical death is prolonged. If measures of resuscitation are not applied in time, however, then autopsy reveals, in this form of death, most severe disorders of the central nervous system.
In this connection, the causes of the extinction of cardiac activity have a certain effect on the duration of clinical death. In cases of electric shock, for example, where cardiac arrest sets in instantly, the period of clinical death can be lengthier than with bleeding.
Age also affects the length of the period of clinical death. The organism of an elderly person, as a rule, survives a shorter period of cardiac arrest than a young and healthy one. Isolated cases have been described in the literature in which it has been possible to bring children back to life after ten and even twelve minutes of clinical death, with complete restoration of vital functions. Nevertheless such long survival of cardiac arrest in humans must be considered rare exceptions, even in young organisms. Changes in the conditions of dying also cause a real effect.
According to the data, the duration of clinical death in dogs is lengthened somewhat by prolonged adaptation to oxygen lack in alpine conditions. Preliminary injection of heparin into the blood, i. e. before the setting in of clinical death, prevents the formation of thrombi during life, and helps subsequent resuscitation, besides leading to a certain prolongation of clinical death.
It should also be noted that the clinical death of a healthy organism, whatever its cause, is more prolonged than that of an organism exhausted by a severe pathological process. For example, the period of clinical death in patients suffering from severe illnesses of the cardiovascular system and respiratory organs is very short.
Terminal states that develop on a background of hypothermia undoubtedly have their own specific features. During dying from blood loss in low temperature conditions, for example, one observes characteristic dynamics in the disturbances of respiration and cardiac activity, and there is an extremely marked tendency of the cardiac muscles to fibrillation, etc. At the same time some of the laws established for dying at normal temperatures, for example the philogenetically based sequence of the extinction and restoration of the various sectors of the central nervous systems, are maintained during dying in conditions of hypothermia.
The main property of hypothermia, increase of the resistance of the higher sectors of the brain to hypoxia through lowering of metabolic processes, and reduction of the energy demands of the organism, creates conditions for more protracted glycolysis and is successfully employed to prolong clinical death, and also as a factor favourably affecting restoration of the higher sectors of the brain.
Experimental investigations carried out in our Laboratory have shown that moderate hypothermia during dying enables the period of clinical death to be prolonged up to an hour. On a background of deep hypothermia the duration of clinical death has been prolonged to two hours. The research of recent years has shown that moderate hypothermia during the restorative period can sometimes help the organism to liquidate the disorders that have arisen during clinical death, even when the length of this period has been as much as six or seven minutes in clinical conditions and ten minutes in experimental ones.