Cardiovascular function during spinal and epidural anaesthesia: pathogenesis, prophylaxis and therapy of complications

5 Cardiovascular function during spinal and epidural anaesthesia: pathogenesis, prophylaxis and therapy of complications J. O. A R N D T P. L I P F E R T

Potentially fatal cardiac arrests occur more often during both spinal and epidural anaesthesia than general anaesthesia (Aubas et al, 1991). Although such mishaps are apparently less frequent now than 20 years ago (Marx et al, 1973), their incidence during major conduction anaesthesia is still one in 10 000, and even one in 7000 in spinal anaesthesia, but only one in 28 000 with general anaesthesia (Olsson and Halldn, 1988). More importantly, healthy young people are also at risk. Under the title 'Unexpected cardiac arrest during spinal anaesthesia' Caplan et al (1988) reconstructed the time course, circumstances and outcome of cardiac arrests in 14 patients, who were on the average 36 years of age, classed as American Society of Anesthesiologists (ASA) category I or II, and who were treated according to presently accepted standards by experienced anaesthesiologists. These cardiac arrests occurred between 12 and 78 min after the start of anaesthesia, with the upper analgesic level at T4 ___1 (_+ standard deviation) and were treated within 1.6+1.9 min. Nevertheless, only four of the patients survived, and these had disabling brain damage. Obviously, spinal and also epidural anaesthesia has a special risk for cardiac arrest even when standard rules are being applied. One wonders therefore why this is so and if the premises on which the currently accepted standards of prophylaxis and therapy rest are still valid. Against the background of recent observations on the extent of sympathetic blockade, the responses of vasoactive hormones and the filling of tile heart during major conduction anaesthesia, we will consider four aspects: 1. 2. 31 4.

The The The The

fundamentals of cardiovascular physiology. cardiovascular effects of spinal and epidural anaesthesia. pathogenesis of cardiovascular complications. prophylaxis and therapy of cardiovascular complications.

Three main conclusions will emerge. Firstly, both spinal and epidural anaesthesia jeopardize primarily the filling of the heart because of blood pooling in the denervated body regions, which is normally counteracted by Bailli~re' s Clinical A naesthesiology--

Vol. 7, No. 3, September1993 ISBN 0-7020-1751-5

641 Copyright9 1993,byBailli~reTindall All rightsofreproductionin anyformreserved

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vasoconstriction in the remaining innervated body regions and particularly by vasoconstriction in the splanchnic region. Secondly, cardiac arrests are likely to occur whenever the filling of the heart is reduced further by blood loss, positive airway pressures, low blood volume states and in certain individuals by vasodilation of the splanchnic vasculature. Thirdly, the prevention of impending and the treatment of manifest cardiac arrests must aim at replenishing the empty heart by counteracting peripheral blood pooling, which is achieved most rapidly and effectively with vasoactive agents, particularly adrenaline (epinephrine USP). FUNDAMENTALS OF CARDIOVASCULAR PHYSIOLOGY Haemodynamics versus haemostatics

The understanding of cardiovascular responses to changing vasomotor tone is greatly facilitated by considering the functional differences between the arterial high pressure system as a bloodflow distributor and the venous low pressure system as a blood volume distributor. In the high pressure system, which comprises the systemic arteries between the left ventricle in systole and the arterioles as the flow resistance section, the pressure is haemodynamic in nature as it depends primarily on blood flow: the flow into (cardiac output) and the flow out of the system through the resistance vessels. As a result, the arterial pressure, which determines the arteriovenous pressure gradient, is generated so that the various organs, connected in parallel, can control their own blood supply by adjusting the internal flow resistance according to their individual metabolic needs. Thus, the arterial high pressure side, where homeostatic control aims at maintaining an appropriate arterial pressure, can be viewed as a flow-

distributing system. Blood pressures in the low pressure system, to which the extrathoracic capacitance vessels and the intrathoracic vasculature including the heart with the left ventricle in diastole belong (Gauer et al, 1970), are haemostatic in nature as they depend primarily on blood volume and its distribution betweeen the intra- and extrathoracic vascular beds that are connected in series by large-bored veins. These connecting veins do not impede blood flow and thus permit rapid volume changes to take place between the two compartments. Because of its rather large compliance (--200 ml/mmHg), the low pressure system holds about 85% of the blood at relatively low pressures; in supine adults, the compliant intrathoracic vasculature (with a compliance of -100ml/mmHg) comprises about 1.5 litres and the extrathoracic capacitance vessels about 3 litres, of which 1.5 litres in each are contained in the vessels of the skeletal muscle/skin and of the splanchnic region. The blood volume in the intrathoracic vasculature varies by several hundred millilitres with everyday changes of body position, respiratory pressures and also peripheral vasomotor tone (Arndt, 1986). However, vasovagal syncope, which may culminate in cardiac arrest, will occur when,

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for whatever reason, the central blood volume is halved in healthy humans (Murray et al, 1968). In essence, the low pressure system may be viewed as the blood-distributing system which subserves the filling of the heart. The regulation of this system aims at constancy of blood volume, not of pressure (Gauer et al, 1970). Neurohormonal control of the circulation

Autonomous nerve system

Major conduction anaesthesia is associated with a conduction block of sympathetic but not vagal efferents. This is noteworthy because vagal tone, for instance, preferentially determines resting heart rate and probably also the vasomotor tone of the splanchnic circulation. Vagal and sympathetic efferents are intermingled in the prevertebral nerve plexus, which may explain why both splanchnic blood flow (Wiklund, 1975) and blood volume (Fujita, 1988) increase during coeliac ganglion blockade, whereas they decrease during major conduction anaesthesia (Kennedy et al, 1970, 1971; Arndt et al, 1985). Vagal drive may therefore contribute to the control of splanchnic blood content, a feature which may bear on the pathogenesis of cardiac arrest (see below). Besides the interplay between vagal and sympathetic influences on certain organs, one must also remember the considerable overlap and divergence of the sympathetic efferents. The preganglionic sympathetic fibres leave the spinal cord via the ventral roots between C8 and L2, but they lose their segmental organization in the paravertebral ganglionic chain, where they travel both cranially and caudally over several spinal segments to eventually synapse with between eight and sixteen postganglionic neurones (Schiffter, 1985). In keeping with the anatomy of the sympathetic system, it has been shown that skin temperature, an indicator of sympathetic blockade, increased in both the hands and the feet, i.e. in the most distant body regions, when sensory block was at or above the T6 spinal segment with lumbar spinal anaesthesia (Chamberlain and Chamberlain, 1986) or at and below T6 with segmental thoracic epidural blockade (Hopf et al, 1990). This suggests that sympathetic functions, i.e. neurogenic vasomotor tone, the release of adrenaline by the adrenals and also the release of renin by the kidney (see below), are impaired, if not completely eliminated, under these circumstances. How and to what extent the blood vessels of various organs would respond to major conduction block are not only questions of sympathetic innervation but also of the type of vessel (contractile muscular versus non-contractile elastic vessels), the investment and density of pharmacological receptors and, in particular, the relationship between neurogenic and basal smooth muscle tone. Arteries. The arterioles, which preferentially control organ blood flow, are equipped with a thick layer of circular smooth muscle cells and also with

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adrenergic nerves and adrenoceptors and are therefore highly contractile and responsive to catecholamines. But it should be noted that the sympathetic tone and the basal tone of vascular smooth muscle differ between organs. Efferent sympathetic tone is highest in skin and skeletal muscle and decreases in the order kidney > intestine > brain > heart and lungs, whereas basal tone, which is also effective in the absence of neurohormonal influences, increases in the opposite direction. One would therefore predict that changes in efferent sympathetic drive would primarily alter the blood flow of skin and skeletal muscle but that there would be little change in other organs.

Capacitance vessels of the low pressure system. By definition, the capacitance vessels comprise the postarteriolar extrathoracic sections, the venules and veins of the systemic circulation, and the sinusoids of the liver and spleen (Arndt, 1986). They contain about two-thirds of the blood, of which several hundred millilitres can be mobilized in favour of the heart. It is noteworthy that the blood-rich veins of skeletal muscle and skin with diameters less than 1 mm are neither invested with circular smooth muscular layers nor are they innervated with sympathetic nerves. Thus, these vessels cannot actively change their calibre, so that their blood content follows passively changes in venous pressures occurring, for example, with changing body position, but also in response to changing flow resistance with resultant change in postarteriolar pressures. Active vasomotor control of filling prevails in the splanchnic circulation, from where several hundred millilitres of blood can be actively mobilized by neurohormonal influences and vasoconstrictor agents, particularly catecholamines with a high affinity for 13-adrenoceptors (Arndt, 1986). Vessels of the pulmonary vasculature. In supine adults the central blood volume, defined as the blood content between the pulmonary and aortic valves, amounts to about 1.5 litres, of which about 80% is held in pre- and postalveolar vessels with diameters greater than 0.2 mm that lack circular smooth muscle layers (Dawson, 1984). Consequently, central blood volume, the ultimate filling reservoir of the left ventricle, cannot be changed actively and therefore must inevitably passively follow filling changes in the extrathoracic capacitance vessels. In essence, the extrathoracic capacitance vessels and the pulmonary vascular bed constitute a functional unit with regard to the distribution of blood; any increase in extrathoracic blood volume leads to a decrease in central blood volume, and vice versa. Vasoactive hormones Physiologically, neurogenic sympathetic influences are important for the control of blood pressure by the rapid adjustment of flow resistance and cardiac output on the one hand and by stabilizing the filling of the heart via their effects on blood distribution on the other. Nevertheless, supine humans can well maintain their circulation even when, for instance, the

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sympathetic nervous system is degenerated (Shy-Drfiger syndrome) or when its influences are eliminated by autonomic blockade, because vasoactive hormones, particularly angiotensin (Ehmke et al, 1987) and vasopressin (Share, 1988), are brought into play as support systems. Angiotensin, the most effective constrictor of resistance vessels, plays a dominant role in the stabilization of blood pressure, whereas vasopressin apparently comes into play as the last line of defence when the filling of the heart is reduced to the extent that cardiac output can no longer be maintained (Quail et al, 1987). The renin-angiotensin system is usually activated first when sympathetic influences are eliminated during blockade of adrenoceptors by the appropriate adrenoreceptor antagonists (Hiwatari et at, 1985; Hasser and Bishop, 1988). This, however, is not so during major conduction anaesthesia because, in this case, the plasma concentrations of renin remain constant while that of vasopressin increase considerably (Peters et al, 1990a; Hopf et al, 1992) (see Figure 1). Thus, an unimpaired neurogenic drive to the BASE

LINE 1

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Figure 1. Arterial blood pressure, vasopressin concentrations and renin activity in the plasma before and after epidural injection of bupivacaine or saline. Values are means _+ standard deviation from seven subjects each. * = P < 0 . 0 5 compared with saline. Note that the fall in arterial pressure during epidural block is associated with a considerable increase in the vasopressin concentration, whereas renin activity is unchanged (Hopf et al, 1 9 9 0 ) .

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kidneys appears to be a precondition for the activation of the reninangiotensin system. Renin, which controls the formation of angiotensin II, originates from the juxtaglomerular apparatus of the kidneys. It is released in response to a fall in arterial pressure, specifically of renal perfusion pressure, but also in response to increased efferent sympathetic drive via [31-adrenoceptors (Ehmke et al, 1987). The latter factor, which is eliminated by epidural anaesthesia, is apparently more important for the release of renin than hitherto believed. It is therefore a special feature of major conduction anaesthesia that the renin-angiotensin system does not respond as a blood pressure support system, not even in the presence of severe hypoxaemia (Peters et al, 1990a). Instead of angiotensin, it is in all like!ihood vasopressin that stabilizes the circulation during major conduction anaesthesia. Vasopressin plasma concentrations not only increase considerably during epidural anaesthesia alone, but even more so when combined with additional challenges such as severe hypoxaemia (Peters et al, 1990a) or head-up tilts (Ecoffey et al, 1985). Finally, that the elevated vasopressin levels do stabilize blood pressure has been proven in dogs in whom arterial blood pressure plummeted during epidural anaesthesia when vasopressin was prevented from acting by pretreatment with a vasopressin I receptor antagonist (Peters et al, 1990b). The distribution of the blood in relation to the heart's filling, the interplay between sympathetic and vagal tone, particularly with regard to vasomotor effects in the splanchnic circulation, and finally vasopressin as a dominant vasoactive hormone are some new aspects which need to be considered when discussing the circulatory effects of major conduction anaesthesia. CARDIOVASCULAR EFFECTS OF SPINAL AND EPIDURAL ANAESTHESIA

Arterial high pressure system Perhaps because the heart receives its sympathetic innervation from the spinal segments T1 to T4, the cardiovascular effects of major conduction anaesthesia are generally said to be more pronounced, particularly with spinal anaesthesia, and the risk for cardiovascular complications are said to be greater when the upper analgesic level exceeds T4 than when the block remains below T4. However, this general view is not supported by the data in Figure 2. In healthy humans, the changes in arterial pressure, heart rate and cardiac output varied in most studies by + 20% of the preanaesthetic controls during both spinal and epidural anaesthesia and regardless of whether or not the upper analgesic level was above or below T4. Note that this is also so with segmental epidural blockade, which definitely eliminates sympathetic drive to the heart, so that bradycardia during major conduction anaesthesia must be of vagal origin.

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Figure 2. The response of cardiovascular variables of the arterial high pressure system to lumbar spinal and cpidural anaesthesia as well as thoracic segmental epidural anaesthesia in healthy subjects (open circles) and premedicated patients and those with concomitant illnesses unrelated to the surgery, mostly arterial hypertension, coronary sclerosis or heart failure (closed circles): averaged data from 56 publications (Lipfert and Arndt, 1993). CNS = central nervous system.

The picture is different in premedicated patients or those with concomitant illnesses unrelated to surgery, mostly arterial hypertension, coronary sclerosis or congestive heart failure. Whereas the heart rate and cardiac output again remained within the ___20% range in this group of people, the arterial pressure was nevertheless substantially lower, particularly when the analgesic level was above T4. It should be stressed, however, that some of this data is from studies published 40 years ago, when 'total spinal anaesthesia' was used to lower blood pressure in the attempt to prevent bleeding during surgery. As expected, blood flow always increased in the denervated extremities, i.e. in the legs and also in the arms provided the upper analgesic level exceeded T4. In contrast blood flow decreased in all other organs, despite the fact that they were deprived of neurogenic sympathetic tone. Why the blood flow of the inner organs decreases rather than increases in response to sympathetic blockade is presently an open question. Alternatives

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are that, compared with the extremities, these organs have a low sympathetic tone, are also under vagal vasoconstrictor tone, respond preferentially to vasoactive hormones or their blood flow decreases because of decreasing arterial pressure. All these alternatives are tenable, but none has been tested experimentally so far. Thus, in healthy humans, changes in blood pressure, heart rate, cardiac output and also organ blood flow remain within the physiological range, regardless of the cranial extension of sensory blockade. The increase of blood flow in the upper extremities is a characteristic feature of conduction blocks at and above the T4 spinal segment, but this is neither accompanied by additional decreases in arterial pressure, heart rate or cardiac output compared with nerve blocks below T4. The T4 dividing line appears to be a rather arbitrary one because we know now that the sympathetic block exceeds the sensory by at least six spinal segments (see earlier), so that sympathetic functions are impaired if not completely eliminated when the analgesic level reaches T6. Finally, even the complete loss of efferent sympathetic drive does not always jeopardize cardiovascular functions in supine humans, apparently because vasoactive hormones, particularly vasopressin, can be called into action. Although premedicated patients and those with certain cardiovascular illnesses are predisposed to respond with a more pronounced fall in arterial pressure, particularly with conduction blockade above T4, there is no conclusive evidence that this would jeopardize the oxygenation of brain and heart (Lipfert and Arndt, 1993) or render these patients susceptible to cardiac arrest because of a loss of cardiac sympathetic tone. The available information on the response of the flow-related variables in the high pressure system do not give a clue to the genesis of cardiovascular complications; bradycardia in particular is not induced by the loss of cardiac sympathetic drive, but the consequence of vagal activation (see below). Low pressure system Only when adequately filled with blood can the heart maintain cardiac output and thus an appropriate arteriovenous pressure gradient, on which depends the blood supply to the organs. Major conduction blockade reduces the heart's filling because it evokes a shift of blood into the denervated body regions. These events easily escape recognition as they are not reflected in flow-related variables but rather in regional changes of blood volume, capacitance and volume-pressure relationships. In the past not much attention has been given to these particular aspects of venous function, perhaps because of the methodological difficulties involved in making volumerelated variables visible, because they are often hidden behind small changes in venous pressure in the rather compliant low pressure system. A case in point is the response of central venous pressure to changing blood volume and vasomotor tone (see Figure 3). Two facts are apparent. Firstly, central venous pressure changes linearly by about 5 mmHg for a blood volume change of 1 litre, giving a total vascular compliance of 200 ml/ mmHg. Secondly at constant blood volume, central venous pressure also

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Figure 3. Changes in central venous pressure in response to changing blood volume and vasomotortone in supine healthymen. Bloodvolumewas altered by haemorrhageand the shed blood retransfused 2 weeks later. Vasomotortone was altered by epidural anaesthesia with 2% lignocaine (lidocaine) or the infusion of noradrenaline (norepinephrine). Note that the central venous pressure changes by 5 mmHg when the blood volume was changed by 1 litre or when vasomotor tone was changed from the quasi-denervated (epidural anaesthesia) to the maximally constricted (noradrenaline infusion) state (Arndt, 1986).

changes by about 5 m m H g between the almost denervated state (epidural blockade) and the maximally constricted state (infusion of noradrenaline [norepinephrine USP]), an effect which is equivalent to a transfusion of 1 litre of blood. Since the pulmonary vasculature cannot actively alter its blood content (see earlier), the observed changes in central venous pressure with changing vasomotor tone must reflect changes in blood volume in the extrathoracic capacitance vessels. Potential blood sources are the mass-rich skeletal muscle and skin and also the splanchnic circulation. In supine healthy adults, these two compartments contain about 1.5 litres of blood each (see earlier), of which about 30% can be mobilized in favour of the heart by neurohormonal influences (Arndt, 1986). How and to what extent changes in vasomotor tone, caused either by major conduction anaesthesia or by vasoactive drugs, alter the regional blood volume, particularly in the heart, can be made visible by sequence scintigraphy, as in Figure 4. The eye-catching feature is the substantial

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Figure 4. Distribution of technetium-labelled erythrocytes before and during epidural anaesthesia: original recording from one subject (body weight 92 kg, upper sensory block at T5) showing whole body images before epidural anaesthesia on the left and during epidural anaesthesia on the right. Increasing darkness in the shading in the various regions illustrates increasing blood content. As an indication of peripheral blood pooling, the dark areas increase in the denervated lower body, most obviously in calves and feet, whereas they decrease in the thorax region, particularly in the heart and curiously also in the denervated splanchnic region (Arndt et al, 1985).

decrease in the heart's silhouette as an indication of its reduced blood content, which is associated with an increase in the blood content of the denervated lower body regions, most obvious in the feet and calves. Note also the reduced silhouette of the liver, which is puzzling because the splanchnic region was definitely deprived of efferent sympathetic drive as the upper analgesic level was at T5 in this case. The relative changes in the distribution of the blood between the functionally most important body regions are shown in Figure 5. As expected, blood content increased in the denervated legs, while at the same time it decreased in all other regions, i.e. in the thorax, the innervated arms and in the denervated splanchnic region. This response pattern was observed in every subject, and also initially in two subjects in whom blood pressure and heart rate later plummeted (for details see below). Thus, during epidural anaesthesia central blood volume, and with it the volume in the heart, is reduced by blood accumulating preferentially in the denervated skeletal muscle and skin regions, as already shown previously by

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Figure 5. The effects of epidural anaesthesia and the distribution of technetium-labelled erythrocytes in supine men. Activity was sampled continuously for 6 min to produce each scan. Changes are expressed as a percentage of the third scan. For estimating the actual regional changes in blood volume, blood was sequestered in both legs (= blood pooling during second scan). Values are means (_+ SE) from eight experiments. During epidural anaesthesia radioactivity increases in the denervated legs but decreases in all other regions, including the thorak and the denervated splanchnic region. Note that blood content in the thorax region decreases more than during blood pooling (Arndt et al, 1985). v e n o u s o c c l u s i o n p l e t h y s m o g r a p h y (de M a r e e s et al, 1976). Since, at t h e s a m e t i m e , b l o o d c o n t e n t d e c r e a s e s in t h e r e m a i n i n g i n n e r v a t e d u p p e r b o d y r e g i o n s a n d , in p a r t i c u l a r , in t h e s y m p a t h e t i c a l l y d e n e r v a t e d s p l a n c h n i c r e g i o n s , o n e m u s t infer t h a t v a s o c o n s t r i c t i o n in t h e s e r e g i o n s helps to stabilize c e n t r a l filling. In h e a l t h y s u p i n e adults, the r e s u l t a n t deficit of the c e n t r a l b l o o d v o l u m e

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J. O. ARNDT AND P. LIPFERT

amounts to approximately 300 ml (Arndt et al, 1985), much like during orthostasis. However, cardiovascular collapse appears to ensue when the vasoconstrictor mechanism in the splanchnic circulation fails so that, due to additional peripheral blood accumulation, the central blood volume is reduced beyond that invoked by blood pooling in the denervated skeletal muscle and skin regions (see below). PATHOGENESIS OF CARDIOVASCULAR COMPLICATIONS

Potentially fatal complications, particularly cardiac arrests, are rather rare and apparently threaten certain individuals, i.e. a small subgroup of patients 3o

20

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Figure 6. Histograms of mean arterial blood pressure before and during major conduction anaesthesia (spinal or epidural) for sensory blockades above and below T4 and thoracic segmental epidural block. Data derived from 12 studies (Lipfert and Arndt, 1993).

CARDIOVASCULAR COMPLICATIONS

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with abnormal responses to major conduction anaesthesia. As a corollary, there seems to be little hope of disclosing the underlying pathomechanism(s) by studying the cardiovascular responses in those subjects who are not susceptible to such complications. Averaged measurements, as in Figure 2, actually obscure the individual responses, a point shown by the histograms in Figure 6. In general, the blood pressures before and the somewhat lower ones during anaesthesia follow a Gaussian-type distribution. However, severe arterial hypotension occurred in a few patients regardless of the extent of blockade, which reflects the singularity of such events. Even though severe hypotension concomitant with bradycardia and symptoms increases in frequency with nerve blockades above T4 (Tarkkila and Kaukinen, 1991; Carpenter et al, 1992), it can also occur at lower levels, as revealed by a number of case reports. Out of 18 patients who had to be treated for severe hypotension with alarming symptoms, the upper analgesic level was above T4 in ten but below T4 in eight (Lipfert and Arndt, 1993). In fact, the block height was also below T4 in at least some of the fatal cardiac arrests mentioned before (Caplan et al, 1988). The T4 level of sensory block is obviously an arbitrary dividing line with regard to cardiovascular complications. Consequently, the cranial extension of blockade above T4, with the resultant loss of sympathetic drive, particularly to the heart, with lumbar techniques and likewise with segmental thoracic epidural blockade is not the only pathogenic factor for complications. One therefore wonders if, for example, the systemic effects of local anaesthetics may be responsible; according to in vitro studies, these decrease in a concentration-related manner the conduction properties as well as the contractility of both myocardium and vascular smooth muscle (Covino, 1987). This, however, is unlikely because quite different plasma concentrations of local anaesthetics, which are much lower with spinal than with epidural anaesthesia, are not associated with differences in the cardiovascular responses. Neither the extent of blockade nor the direct effects of local anaesthetics can explain the occurrence of life-threatening cardiovascular complications. Therefore, in view of the singularity and rareness of such events, they are probably a manifestation of an individual predisposition, possibly because of an inherent dysfunction of cardiovascular control mechanisms in the absence of sympathetic influences, and probably involving activation of vagal drive via either the cortex of the brain or a reflex from the empty heart. Activation of the vagus via the brain

A number of symptoms such as ostensive bradycardia with a consequent drop in arterial pressure, profound sweating, nausea, and eventually vomiting accompany cardiovascular complications during major conduction anaesthesia. This pattern, which is believed to reflect an activation of vagal efferents, resembles vasovagal syncope, of which certain individuals suffer in response to unpleasant emotions, particularly fright. That such responses may be facilitated when sympathetic tone is impaired during major conduction anaesthesia is at least plausible.

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A case in point is the report f r o m a healthy y o u n g and sporty physician w h o u n d e r w e n t epidural anaesthesia w i t h o u t p r e m e d i c a t i o n for k n e e surgery. A t first, the anaesthesia was uneventful, but w h e n told that the condition of the k n e e w o u l d not permit participation in sports in the future, the patient s u d d e n l y suffered a cardiac arrest requiring resuscitation (Frerichs et al, 1988). T h e authors speculated that possibly the passivecoping situation of paralysis activates the vagus, unlike in active-coping situations w h e n s y m p a t h e t i c activation p r o m o t e s an e s c a p e r e s p o n s e . Reflex vagal activation f r o m the heart

Vasovagal syncope of central origin is characterized by its suddenness, whereas that of cardiac origin usually has a slower time course, as the synopsis of such events in Figure 7 shows. In healthy supine men with intact innervation, the gradual reduction of central blood volume initially evokes, amongst other effects, an increase in heart rate by a reflex activation of sympathetic tone, so that blood pressure remains by and large constant except for the continuously decreasing pulse pressure as a consequence of reduced stroke volume due to central hypovolaemia. However, as soon as central blood volume is about halved, the tachycardia suddenly turns into bradycardia, with a further narrowing of pulse pressure which culminates in n=20

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Figure 7. Time course of arterial blood pressure, particularly pulse pressure, and heart rate in supine healthy men and patients in response to central hypovolaemia: the left-hand figures show circulatory response to graded reduction of central blood volume with intact innervation denoting gradual central hypovolaemia evoked by the application of negative pressures to the body regions below the xyphoid; the figures in the centre show spinal anaesthesia in patients with severe arterial hypotension and/or bradycardia with symptoms of incipient faint, detailing the time course of impending cardiovascular collapse during spinal anaesthesia; and the right-hand graphs highlight the time course of blood pressure and heart rate until cardiac arrest during spinal anaesthesia. Note the cardiovascular response pattern to induced central hypovolaemia and spinal anaesthesia is similar. Note also that bradycardia with decreasing pulse pressure develops slowly over a time period of 10-20 min before cardiovascular collapse or cardiac arrest occur.

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syncope with loss of awareness in all subjects and a temporary cardiac arrest in one case which lasted for 9 s (Murray et al, 1968). The same pattern was seen in patients during spinal anaesthesia who were either treated because of impending cardiovascular collapse or who actually suffered a cardiac arrest. The slowly decreasing pulse pressure as a reliable indicator of impaired cardiac filling, and the accompanying decrease in heart rate, are the characteristic features of impending cardiovascular collapse during spinal anaesthesia. These changes develop over a time period of about 10-20 min and can be recognized when heart rate and blood pressure, particularly pulse pressure, are measured at least every 5 min, the alarming combination being bradycardia with reduced pulse pressure. Evidently, the maintenance of cardiovascular stability is intimately linked with the blood volume in the heart which, when depleted beyond the physiological limit, leads inevitably to cardiac arrest. The underlying mechanisms have been analysed in some detail in animals which respond similarly to central hypovolaemia. It is a reflex activation of vagal efferents with a concomitant inhibition of sympathetic drive that leads to severe bradycardia and peripheral vasodilation, particularly in the splanchnic region, a response pattern referred to as the Bezold-Jarisch effect (Mark, 1983; Ludbrook, 1990). As has been pointed out earlier, major conduction anaesthesia always reduces cardiac filling, but not usually below the physiological limits. However, any additional depletion of the heart will spell danger. For example, in healthy supine men, severe arterial hypotension and even cardiac arrest could be evoked during epidural anaesthesia by a blood loss of only 0.75 litres (Bonica et al, 1972) or by continuous positive pressure breathing at + 10 mmHg (Stfihmeier et al, 1991). Also, patients with certain forms of arterial hypertension, such as phaeochromocytoma, with low blood volumes do not tolerate major conduction anaesthesia. Finally, bed-ridden patients are perhaps prone to cardiovascular complications as the blood volume is already reduced by 0.5 litres after only 3 days of bed rest and by as much as 1 litre after 28 days (Miller et al, 1965). Such detrimental interactions are to be anticipated and can usually be prevented by appropriate prophylaxis, so that cardiac arrests which occur under such circumstances are not unexpected. However, cardiac arrests in seemingly healthy young individuals with sensory block heights below T4 are unexpected. In such rare cases, an inherent dysfunction of splanchnic vasomotor control appears to play a role as a pathogenic factor. This came to light by accidental observations in two subjects who suffered severe arterial hypotension with bradycardia and symptoms such as profound sweating, nausea, restlessness and impaired awareness during epidural anaesthesia. In these two subjects, unlike in others with stable blood pressure, the blood content in the splanchnic vasculature increased while the central blood volume decreased further to the lowest levels found in the study (see Figure 8). The reason for this secondary vasodilation of the splanchnic circulation is not clear at present, but perhaps results from an activation of vagal efferent drive in the absence of sympathetic tone (Arndt et al, 1985). But whatever the underlying mechanism may be, it is apparently an individual

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predisposition, i.e. an inherent dysfunction of vasomotor control of the splanchnic vasculature, which presently cannot be diagnosed so that the occurrence of such events cannot be predicted. PROPHYLAXIS AND THERAPY OF CARDIOVASCULAR COMPLICATIONS Both prophylaxis and therapy should aim primarily at stabilizing or replenishing cardiac filling, but not just at preventing the usually harmless decreases in arterial blood pressures. Principally, this can be achieved either by increasing blood volume or by counteracting vasodilation in the sympathicolytic regions with vasoconstrictor agents. The latter principle was employed to advantage until the late 1960s, but then 'volume loading' came into fashion, curiously, without evaluation of its efficacy. The available information casts serious doubt on whether 'volume' prophylaxis as currently employed would stabilize blood pressure and prevent cardiovascular complications. For example, during spinal anaesthesia blood pressure decreased equally regardless of prophylactic electrolyte infusion of 1 litre, though with some delay in the pretreated group (Venn et al, 1989). Not even the prophylactic infusion of colloid solutions prevented the blood pressure

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from falling (Lipfert and Arndt, 1993). More importantly, cardiac arrests occurred in healthy young patients who had received on average nearly 1 litre of an electrolyte solution (Caplan et al, 1988). In 952 spinal anaesthesias, the prophylactic infusion of 0.5 litres of fluid did not alter the incidence of arterial hypotension and bradycardia. However, there were no side-effects at all in those patients who had received either ephedrine infusions or injections of atropine or glycopyrrolate, which let the authors conclude 'that our incidences of hypotension and bradycardia may have been higher without the prophylactic use of these drugs' (Carpenter et al, 1992). In other words, had all patients been given 'these drugs' the incidence of complications would have been lower. There is indeed ample evidence that prophylaxis with various vasoconstrictor agents stabilizes blood pressure. This has been shown for a number of catecholamines (Dripps and Deming, 1946; King and Dripps, 1950), but also for vasopressin (Dripps and Deming, 1946) and for dihydroergotamine (Klingenstr6m, 1960; Hilke et al, 1978), an alkaloid with venoconstrictor properties. Since the stabilization or re-establishment of appropriate cardiac filling by preventing or reversing peripheral blood pooling during major conduction anaesthesia is the primary aim of both prophylaxis and therapy, it is of some interest that certain vasoactive agents mobilize substantial volumes of blood from different sources in favour of the heart. Dihydroergotamine, for example, preferentially constricts capacitance vessels of skeletal muscle and skin and thus reverses the blood pooling effects of major conduction anaesthesia, whereas catecholamines, particularly those of the adrenaline-type, selectively constrict the splanchnic vasculature, where additional blood may accumulate in certain individuals. At therapeutic doses, each agent may mobilize approximately 300 ml of blood in adults, which is equivalent to a blood transfusion of 0.6 litres or of even 1.2 litres when the two act together (Arndt et al, 1985; Stanton-Hicks et al, 1987). This way the heart can be replenished within seconds or a few minutes at the most, certainly quicker than with intravenous fluid infusions. Catecholamines, with their short-lived action, are certainly the agents of choice for the therapy of manifest cardiovascular complications, whereas dihydroergotamine has an advantage for prophylaxis because of its prolonged action of at least 1 h (Hilke et al, 1978). The efficacy of dihydroergotamine has been compared with that of volume loading (Ringer's lactate 10 ml/kg prior to anaesthesia) in a prospective placebo (no prophylaxis) controlled study on 1066 patients during spinal anaesthesia; the results are given in Table 1. Consistent with others (Caplan et al, 1988; Carpenter et al, 1992), the incidence of complications is about 20% and they occur up to at least 60 min after the start of anaesthesia. Dihydroergotamine reduced the incidence of complications more than volume loading, particularly the late ones, whereas 'volume' is effective only during the first 15 min of anaesthesia. Prophylaxis with dihydroergotamine is superior to volume loading, but neither one prevents complications with certainty. Thus the monitoring of blood pressure and heart rate at least every 5 min is presently the safest way to recognize incipient cardiovascular complications.

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Impending circulatory arrests and symptoms of vagal hyperactivity may also be treated by atropine, which may reverse not only the bradycardia but possibly also the vasodilation in the splanchnic region. However, catecholamines, particularly adrenaline, are the first choice for therapy of manifest cardiac arrests, not only because they rapidly replenish the heart but also because they increase the contractility of the myocardium and of the resistance vessels. This notion is also supported by the course of events in the treatment of cardiac arrest during spinal anaesthesia where the circulation was restored only after the injection of adrenaline, but perhaps too late (Caplan et al, 1988). With regard to the therapy of complications it should be remembered that 'CPR (cardiopulmonary resuscitation) is ineffective when there is no blood in the heart' (Keats, 1988). SUMMARY

Both spinal and epidural anaesthesia are fraught with a high risk for lifethreatening cardiovascular collapse and also fatal cardiac arrests, the incidence of which is higher than with general anaesthesia. These mishaps also endanger young people with sensory block below the T4-T5 range and in spite of appropriate care according to presently accepted standards. With regard to the pathogenesis and also the prophylaxis and therapy of such events, some new information has been considered: 1.

2. 3.

4.

Sympathetic neurogenic control of the circulation is impaired, if not completely eliminated, when sensory blockade is above the T6 level (lumbar techniques) or below T6 (segmental thoracic epidural anaesthesia). Major conduction anaesthesia prevents the renin-angiotensin system from acting, so that cardiovascular stability depends entirely on vasopressin. Major conduction anaesthesia primarily reduces central blood volume and thus the heart's filling because of blood pooling in the denervated muscle and skin regions, an effect which is counteracted by vasoconstriction in the remaining innervated body regions and, in the vast majority of people, by constriction of the splanchnic vasculature. Cardiovascular collapse may occur whenever the filling of the heart is further reduced, such as by blood loss, positive airway pressure, or low blood volume states as in certain forms of arterial hypertension or in bed-ridden patients, and also when the vasoconstrictor mechanism of the splanchnic circulation fails in certain individuals with an inherent dysfunction of splanchnic vasomotor control.

The prophylaxis and therapy of cardiovascular complications during major conduction anaesthesia must primarily be aimed at stabilizing or reestablishing appropriate cardiac filling by an increase in either blood volume or vasomotor tone. There is convincing evidence that the efficacy of vasoconstrictor prophylaxis in preventing cardiovascular complications is by far superior to volume prophylaxis as currently employed.

660

J. O. ARNDT AND P. LIPFERT

T h e t r o u b l e spot of m a j o r c o n d u c t i o n b l o c k a d e resides in the filling of the heart. V a s o c o n s t r i c t o r agents in g e n e r a l a n d c a t e c h o l a m i n e s of the a d r e n a l i n e - t y p e in p a r t i c u l a r m o b i l i z e rapidly (within a few m i n u t e s at the most) s u b s t a n t i a l v o l u m e s of b l o o d f r o m the p e r i p h e r a l v a s c u l a t u r e in f a v o u r of the heart. V a s o c o n s t r i c t o r s are t h e r e f o r e the first choice for the prophylaxis a n d t h e r a p y of cardiovascular c o m p l i c a t i o n s d u r i n g m a j o r cond u c t i o n a n a e s t h e s i a . It s h o u l d be r e m e m b e r e d that c a r d i o p u l m o n a r y resuscitation is ineffective w h e n t h e r e is n o b l o o d in the heart.

REFERENCES

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cardiovascular variables after spinal anaesthesia with glucose-flee 0.75% bupivacaine. British Journal of Anaesthesia 63: 682-687. Wiklund L (1975) Postoperative hepatic blood flow and its relation to systemic circulation and blood gases during splanchnic block and fentanyl analgesia. Acta Anaesthesiologica Scandinavica Supplement 58: 5-29.