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ANAESTHESIA AND THE CARDIOVASCULAR SYSTEM

J.J. Walton & A.M. Cohen

Central nervous system (CNS) depression is the goal of general anaesthesia. In practice, however, this is accompanied by effects on other organ systems particularly the respiratory and cardiovascular systems (CVS). diminishes Ca2 -induced Ca2 release from the sarcoplasmic reticulum (SR), leaving less Ca2 to bind to the myocardial muscle filaments. In vitro, halothane also inhibits a cell membrane Na Ca2 exchange pump; further diminishing Ca2 flux independently of T- and L-type Ca2 channels. The net effect is depressed contractility and CO.

Pharmacological agents
Inhalational agents Cardiac contractility
All fluorinated agents reduce cardiomyocyte Ca2 influx. A lower cytoplasmic Ca2 concentration
PHARMACOLOGICAL Anaesthetic agents exert their effects on the CVS in a variety of ways:

Vascular smooth muscle

Isoflurane, sevoflurane and desflurane cause greater decreases in SVR than enflurane or halothane. In
NON-PHARMACOLOGICAL Effects mediated by baroreceptors, chemoreceptors and ANS.

Direct Cardiomyocyte depression contractility and conduction Vasomotor tone in coronary and systemic circulations Indirect Release of vasoactive substances (e.g. histamine) Sensitization of the heart to endogenous catecholamines Autonomic nervous system (ANS) depression

Tracheal intubation/extubation Increased HR, increased contractility and vasoconstriction via the sympathetic nervous system; vagal bradycardia may occur Intermittent positive-pressure ventilation (IPPV) Impaired venous return leading to decreased SV Hypercarbia Increased HR, increased contractility and vasoconstriction via central chemoreceptors Patient positioning Changes in venous return

Ca2 T T
Halothane

Ca2 T T

ICaT

ICaT

0 mV ICaL Figure 7.1 The effect of halothane on cardiomyocyte Ca2 channels. Reduced Ca2 influx via T- and L-type results in slowing of AP conduction and reducing the rate of pacemaker AP generation.

60

ICaT Halothane binds L- and T-type Ca2 channels Time

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the coronary circulation isoflurane produces dosedependent vasodilatation primarily in the small, highresistance arteries (similar to SNP) while halothane exerts its vasodilatory effect on the large, low-resistance vessels (similar to glyceryl trinitrate) (Table 7.1).

levels during laryngoscopy or surgical stimulation may cause VT or VF.

The diseased heart

Most studies indicate that inhalational anaesthetics induce a degree of coronary vasodilatation. With the exception of isoflurane and desflurane, changes in coronary blood flow are in proportion to oxygen demand (MVO2) autoregulation is maintained (Figure 7.2). There is little evidence that clinically relevant doses of inhalational anaesthetics have a deleterious effect on the diseased heart. However, in the case of desflurane associated sympathetic activity has been shown to worsen myocardial ischaemia in patients undergoing coronary artery surgery.
60
1)

Heart rate and cardiac conduction

The volatile agents have both direct and indirect effects on HR and conduction. With the exception of desflurane, which produces hyperactivity at 0.52.0 MAC, other volatile agents depress sympathetic activity. In addition, baroreceptor-mediated reflex tachycardia, secondary to reduced SVR and contractility, is blunted by CNS depression and slowed conduction. Even at low concentrations, halothane directly binds to T- and L-type Ca2 channels in the cell membranes of cardiomyocytes, diminishing Ca2 influx. SA nodal pacemaker action potential (AP) generation is slowed or abolished (Figure 7.1), atrioventricular (AV) nodal AP transmission is slowed and the refractory period is increased. Conversely, in the HisPurkinje system halothane slows AP conduction, increases AP duration and shortens the refractory period. If the SA node is inactive, other more slowly discharging foci in the atria or near the AV junction may emerge as pacemakers, increasing the risk of dysrhythmia. Volatile agents (particularly halothane) are more likely to cause dysrhythmias in the presence of circulating catecholamines. In the presence of halothane, the competing effects of 1A-adrenoceptor stimulation (reducing HisPurkinje AP conduction velocity) and -stimulation (increasing conduction velocity between Purkinje cells and myocytes), produces re-entrant circuits in the ventricular muscle with the potential to cause extrasystoles. While innocuous dysrhythmias are common, acidosis, hypokalaemia and hypocalcaemia may cause malignant dysrhythmias, such as bigeminy and multifocal ventricular extrasystoles. Sudden fluctuations in serum raised catecholamines

Adenosine Isoflurane

Cerebral blood flow (ml min

45 Awake Enflurane 30 Halothane 15

20 40 60 80 Diastolic pressure (mmHg)

100

Figure 7.2 Schematic representation of the relationship between coronary blood flow and diastolic arterial pressure. Secondary to decreased MVO2, halothane and enflurane shift the autoregulation curve to the right (coronary sinus oxygen saturation practically unchanged), whereas isoflurane (and desflurane) shift the curve to the left and straighten it. The effect of adenosine, the most potent coronary vasodilator, is shown for comparison.

Table 7.1 Effects of volatile agents on the CVS Properties HR / MAP CO Slight SVR Catecholamine sensitization /

Halothane Nitrous oxide Enflurane Isoflurane Desflurane Sevoflurane

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Coronary steal
Steal is defined as an increase in flow to a normally perfused area following coronary arteriolar vasodilatation at the expense of a decrease in perfusion to a collateraldependent area. The prerequisite conditions for this phenomenon are (Figures 7.3 and 7.4) as follows:

to the increase in MVO2 caused by changes in HR and SVR.

Nitrous oxide
Nitrous oxide (N2O) produces modest dose-dependent cardiac depression. Unlike other inhalational agents this effect is offset by an increase in SVR secondary to sympathetic stimulation. The addition of N2O to a volatile anaesthetic has been shown to result in less depression of arterial pressure than with volatile alone.

Total occlusion of the artery supplying the stealprone area. Perfusion of steal-prone area dependent on collateral vessels. 90% stenosis in the artery supplying the collaterals.

Intravenous agents
There is little evidence that any of the IV anaesthetics have a direct effect on the human cardiac conducting system. Dysrhythmias may however occur as a result of reduced myocardial blood flow and reflex tachycardia.

Although isoflurane-induced coronary steal has been demonstrated in animal models there is little evidence for it in humans, indeed recent studies suggest that isoflurane improves ischaemia in some patients with ischaemic heart disease and has myocardial protective properties. It seems likely that when ischaemia has been seen in association with isoflurane, it is related
Collateral supply artery

Barbiturates
Thiopental remains the worlds most widely used IV anaesthetic agent and is the only barbiturate in common

Supply artery

51%

10%

16%

23%

Figure 7.3 The four angiographic anatomical variants defined by the Coronary Artery Surgery Study (CASS) Registry. Total occlusion of a vessel associated with 50% stenosis in the collateral supply vessel was demonstrated in 23% of angiograms. However, only 12% of the 16,249 angiograms studied met the criteria for steal-prone anatomy 90% stenosis of the collateral supply artery. Inital state Occluded supply artery 20 mmHg 100 mmHg 80 mmHg Vasodilator 100 mmHg Stenosed collateral supply artery 50 mmHg

Steal-prone (ischaemic) area

20

70 70 70 (b)

10

200 300 100

(a)

Figure 7.4 Proposed mechanism of vasodilator-induced coronary steal. In the initial state (a) a collateral supply vessel pressure of 80 mmHg (distal to the stenosis) generates a perfusion pressure of 20 mmHg in the steal-prone (ischaemic) area. Following vasodilator administration (b) increased blood flow to the non-ischaemic area reduces perfusion pressure in the steal-prone area to 10 mmHg.

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use in the UK. The CVS effects include direct cardiac depression and vasodilatation. In contrast to the inhalational agents, the CVS effects are more patient dependent. In young healthy subjects, CVS effects are limited to a modest fall in SVR and cardiac contractility, both compensated for by a baroreceptormediated increase in sympathetic tone response. In the elderly and in patients with hypovolemia or decreased cardiac reserve, a profound fall in SVR and SV may occur.

Opioids
Opioids are discussed in Chapter 13.

Neuromuscular blockers Suxamethonium

The structural similarity to acetylcholine accounts for direct agonist action on the ANS and its effects on the CVS. Increased sympathetic tone leads to tachycardia and increased SVR, which may be exacerbated by subsequent endotracheal intubation. The resultant rise in myocardial MVO2 is undesirable and may worsen the pre-existing ischaemia. In some patients administration of the drug can lead to severe bradycardia due to a direct muscarinic effect. Bradycardia is most commonly seen in children and with repeat dosing.

Etomidate
Etomidate is the most cardiovascularly stable of the IV induction agents. Depression of the adrenocortical axis limits its clinical use.

Ketamine
The effects of ketamine on the CVS differ from those of other agents. It is the only general anaesthetic in current usage that does not produce CVS depression in patients with intact autonomic function. Modest direct myocardial depression is offset by its centrally mediated sympathomimetic actions leading to tachycardia, vasocontriction and hypertension, which in turn increase myocardial oxygen demand. In patients with impaired autonomic function however, the direct cardiac depressant effects may predominate producing cardiovascular collapse.

Non-depolarizing drugs
Steroid and bis-quaternary ammonium non-depolarizing muscle relaxants (NDMRs) may exert CVS side-effects by histamine release or actions on the autonomic ganglia effects or vagus nerve. Histamine release is most commonly seen with atracurium. The effect is idiosyncratic. D-tubocurarine, noted for its propensity to cause a profound autonomic ganglionic blockade, is rarely used nowadays. Clinically significant ganglionic blockade is not associated with conventional doses of commonly used NDMRs. Pancuronium has vagolytic properties, which combined with a low propensity to cause histamine release account for its enduring popularity with cardiac anaesthetists. It can counteract some of the unwanted effects of other anaesthetic drugs notably bradycardia. Rapid administration may cause profound tachycardia.

Propofol
Owing to its pharmacokinetic profile, propofol has become the most commonly used IV induction agent in the developed world. It has a cardiac profile very similar to that of thiopental, despite initial claims that it had minimal CVS effects. It causes direct cardiac depression and vasodilatation. Tachycardia occurs less frequently than that following thiopental administration. The deleterious CVS effects can be minimized by slow titration of the drug to observed effect.

Regional anaesthesia
The CVS effects of regional anaesthetic techniques are the result of sympathetic blockade or inadvertent IV injection of local anaesthetic drugs.

Benzodiazepines
Diazepam, lorazepam and midazolam are often used as adjuncts to cardiac anaesthetic techniques. Although all cause hypotension secondary to myocardial depression and vasodilatation, the magnitude is less marked than that seen with barbiturates and propofol. Lorazepam has little effect on HR whereas midazolam and diazepam may be associated with either bradycardia or tachycardia. Midazolam causes a more pronounced CVS depression reflecting its faster action.

Local anaesthetic agents

Local anaesthetics block Na channels in excitable tissue, both neuronal and non-neuronal. All can be thought of as negatively inotropic and antidysrhythmic. Lidocaine has a well-known role as a Vaughan Williams Class 1 antidysrhythmic. It is relatively safe

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because of its low potency and tissue binding; consequently, a high serum concentration is necessary before cardiac toxicity is seen. Tinnitus, dizziness and perioral paraesthesia all of which occur at lower concentrations act as early warnings of misadministration in the conscious patient. Bupivacaine has a narrower margin of CVS safety. Although greater tissue binding reduces the likelihood of CNS effects if used appropriately, inadvertent IV administration causes significantly greater problems. Firstly, its longer duration of action tends to cause, rather than suppress, dysrhythmias. Secondly, it has a direct toxic effect on cardiomyocyte contractile function. The overall effect of a significant IV dose of bupivacaine is refractory cardiac collapse that is only partially treatable with sympathomimetics. Identification of D-bupivacaine as the more cardiotoxic isomer has led to the introduction of laevo (S-) bupivacaine, which has been shown to have a lower cardiac toxicity.

vasodilatation, as they are unable to increase stroke work to compensate for the drop in SVR. Spinal anaesthesia is contraindicated in these patients. In most other patients the adverse CVS effects of spinal and epidural blockade can be prevented or treated by the administration of IV fluids and direct-acting sympathomimetics such as ephedrine or -adrenoceptor agonists like phenylephrine.

Key points

The CNS effects of general anaesthesia are mirrored in other organ systems. The CVS effects of anaesthetic agents are dependent on patient age and physiological status. Anaesthetics have both direct and indirect actions on the CVS. Direct myocardial and vascular depression is often compensated for or obscured by autonomic reflexes.

Sympathetic effects
All forms of regional anaesthesia have the potential for ANS blockade. Spinal anaesthesia causes a more rapid sympathetic blockade than epidural anaesthesia reflecting its faster onset. The extent of the CVS effects (primarily decreased vascular tone) is directly related to the type of block used (spinal epidural), the dose of local anaesthetic used and the extent to which haemodynamic stability is dependent on sympathetic tone. Patients with so-called fixed CO states such as severe aortic stenosis are particularly susceptible to sudden

Further reading
Agnew NM, Pennefather SH, Russell GN. Isoflurane and coronary heart disease. Anaesthesia 2002; 57: 338347. Ebert TG, Muzi M. Sympathetic hyperactivity during desflurane anaesthesia in healthy volunteers. A comparison with isoflurane. Anesthesiology 1993; 79: 444453. Priebe H-J. Isoflurane and coronary hemodynamics. Anesthesiology 1989; 71: 960976. Rusy BF, Komal H. Anaesthetic depression of myocardial contractility: a review of possible mechanisms. Anesthesiology 1987; 67: 745766.

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