Thoracic Epidural Anesthesia and the Patient with Heart Disease

In the Western world, cardiovascular morbidity is the most common primary cause of death 1,2. Coronary artery disease is a widespread concomitant condition in patients undergoing surgery 1,3. The patient with coronary artery disease is susceptible to myocardial infarction, dysrhythmias, ventricular failure, and cardiac death 1. Patients with chronic cardiovascular disease have a high risk of adverse cardiac outcome after surgery, especially after acute perioperative ischemic events 4. The optimal anesthetic and analgesic management for these patients remains undefined 5. Numerous studies have shown that stimulation of the sympathetic nervous system plays a major role in the development of perioperative myocardial ischemia 6-9. Activation of cardiac sympathetic efferents may reduce myocardial oxygen availability by inducing poststenotic coronary constriction 10, which can lead to redistribution of myocardial blood flow with a reduction of blood supply to the subendocardium. Myocardial oxygen consumption is increased by tachycardia and increased contractility. This mismatch between oxygen delivery and demand during sympathetic activation can lead to myocardial ischemia, decreased arrhythmia threshold, and ventricular failure. In several patient populations with a high prevalence of coronary artery disease (such as peripheral vascular disease), the use of regional anesthesia has been investigated to improve outcome 11-13. Thoracic epidural anesthesia (TEA) aims at a more specific reversible blockade of cardiac sympathetic efferents and afferents and provides intra- and postoperative analgesia or-in the nonsurgical population-effective therapy of anginal pain 14. This review focuses on TEA and does not examine studies of lumbar epidural anesthesia and cardiac outcome in detail. Physiology and Pathophysiology In a resting adult who weighs 70 kg, coronary blood flow (CBF) is approximately 225 mL/min, which is approximately 4%-5% of cardiac output. In the autoregulatory range, CBF is nearly constant over a wide range of perfusion pressures. At a constant myocardial oxygen consumption, a decrease in coronary perfusion pressure causes autoregulatory vasodilation, adjusting coronary vascular resistance to maintain constant myocardial perfusion 15 (Figure 1). The major variables that influence coronary flow are perfusion pressure, myocardial systolic compression, metabolic control, and neurohumoral factors 16. Beyond the autoregulatory range, coronary perfusion is proportionally related to coronary perfusion pressure and inversely dependent on coronary vascular resistance. Under these circumstances, changes in mean arterial pressure (MAP) are usually followed by a proportional change in CBF. Coronary perfusion pressure is often defined as the difference between MAP and left ventricular end-diastolic pressure. Because nearly 70% of CBF occurs during diastole, and increases in heart rate are accompanied by a shortening of the duration of diastole, heart rate is also an important determinant of CBF.Figure 1: Normal coronary blood flow (CBF) autoregulation at a constant myocardial oxygen consumption in dogs. The zone in which autoregulation is intact represents the pressure range at which CBF remains nearly constant as coronary pressure changes. Coronary vascular reserve is the difference between the lower curve and the straight maximum vasodilation line modified from [15].Neural effects on cardiac performance and rhythm are mediated via alpha- and beta- adrenergic receptors. Sympathetic alpha-adrenergic stimulation leads to a vasoconstrictive influence on epicardial vessels, in which alpha-receptors dominate. Moreover, this vasoconstrictive activity limits vasodilation in the subepicardial vessels and prevents epicardial steal. In healthy subjects, this stimulation does not necessarily lead to an increase in coronary vascular resistance, because metabolic counter-regulation may mobilize substantial vasodilatory reserve, especially in the subendocardial tissue 17. Intramyocardial and subendocardial coronary arteries are dominated by beta1-adrenergic receptors 18-20. The effect of beta-adrenergic stimulation of coronary vessels is not clearly defined because multiple effects are mediated by beta-receptors in vivo. beta-stimulation causes positive inotropy and chronotropy, which leads to increased myocardial metabolism and oxygen consumption. Because perfusion and contraction are coupled, an increased myocardial metabolism is followed by an increase in CBF via metabolic regulation 21. The exact mechanism of metabolic regulation remains controversial; adenosine triphosphate-sensitive K+-channel openers 22, adenosine 23, prostaglandins 24, neuropeptides 25, and nitric oxide 26 are involved. An overview of these mechanisms exceeds the scope of this review. Counteracting the stimulation of beta-receptors with beta-blockade in resting dogs, however, results in a decreased CBF, whereas the oxygen delivery/oxygen consumption ratio remains constant. Decreased CBF might be the result of reduced myocardial oxygen consumption 27. The effects of sympathetic stimulation in patients with coronary artery disease differ from those in healthy subjects. Nabel et al. 10 have demonstrated that constriction of atherosclerotic arteries is induced by the cold-pressor test, whereas smooth segments are dilated. This effect of sympathetic activation agrees with the finding in patients with classic angina that the diameter of the atherosclerotic artery decreases during exercise 28. Activation of sympathetic influences can also override local metabolic vasodilation, which has been shown for adenosine infusion 29 or stress, induced by the cold pressor test 30. This might be caused by activation of alpha-receptors 31, which restrict the metabolically related flow increase by approximately 30% 32. Besides sympathetic reflexes, the endothelium plays an important role in the tone of coronary arteries 33. In animal studies, it has been demonstrated that after removal of the endothelium, the relaxing effects of beta-adrenergic agonists are reduced and the constrictive effects of alpha-adrenergic agonists are enhanced 34,35. Therefore, dysfunction of the endothelium can have further deleterious effects in the mediation of sympathetic activity. High TEA has the potential for blocking cardiac afferent and efferent fibers, which originate from the first to fifth thoracic level (T1-5) 36. The perception of cardiac pain and angina is mediated via sympathetic afferent nerves. Stimulation of sympathetic efferents leads to an increase of inotropy, cardiac output, and systemic vascular resistance (Figure 2). Epidurally applied local anesthetics targeted to the T1-5 segments produce sensory blockade, motor blockade (depending on concentration), and blockade of the cardiac sympathetic fibers. In patients with coronary artery disease, it has been reported that TEA leads to a reduction in heart rate, cardiac output, and systemic vascular resistance, it may therefore decrease myocardial oxygen demand 37,38. However, others reported increased heart rates with reduced cardiac output 39 or no change in either value 40,41. The effect of TEA on left ventricular contractility has been the subject of several animal and clinical studies, but it still remains controversial. Contractility has been reported to be unchanged 42,43, reduced 44-46, or improved 47,48. The variability of these results might be due to the different types of anesthetics used, whether epinephrine was added, the differing number of segments blocked, and species differences.Figure 2: Schematic illustration of the cardiac sympathetic innervation. a, Sympathetic stimulation in the thoracic region (Th1 to Th5) leads to an increase in heart rate, inotropy, and metabolism. b, Lumbar sympathetic innervation targets intraperitoneal and retroperitoneal organs and sympathetic stimulation of this area results in a decrease of motility.Various variables have been used to measure left ventricular function, including isovolumetric and ejection phase indices such as dP/dtmax, stroke volume, systolic time intervals, or ejection fraction. All these variables are highly dependent on cardiac loading conditions 49. In conclusion, positive effects of TEA cannot simply be deduced from these investigations, and differences in patient populations must be taken in account when evaluating studies of TEA. Ideally, in patients at risk of ischemia, TEA should dilate constricted coronary vessels, decrease heart rate and myocardial metabolism, and improve cardiac function by reducing pre- and afterload and optimizing oxygen availability. In general, hemodynamic stability and a reduced stress response should provide an improved outcome, although hypotension can occur after epidural blockade of T1-S5 segments by diminishing sympathetic counter-regulation in a substantial vascular reservoir 50, which may offset the positive hemodynamic effects of TEA. Epidural Anesthesia and Pathologic States of the Heart It has been well established that activation of the sympathetic nervous system plays an important role in the pathophysiology of myocardial infarction, angina pectoris, and fatal cardiac arrhythmias 6,8,9. Conversely, inhibition of sympathetic stimulation can reduce cardiac morbidity 7,51. Selective inhibition of the sympathetic nervous outflow to the heart can be achieved by TEA, which blocks the segment T1-5, and although oxygen supply to the ischemic myocardium is improved, total CBF is unaltered. In experimental settings, the ratio of endocardial to epicardial blood flow is increased 43,52, and blood flow to ischemic regions is improved 52. Under the influence of TEA, the size of the infarcted area was smaller both in subepicardial and subendocardial regions after experimental coronary occlusion in dogs (Figure 3) 44. However, this investigation was not conclusive, because TEA decreased the rate-pressure product (RPP), which is usually beneficial in myocardial ischemia. A study with equivalent hemodynamic conditions induced by beta-adrenergic blockers has not been performed. After myocardial stunning, recovery was significantly faster in dogs when the ischemic insult leading to the stunning was induced during TEA under equivalent hemodynamic conditions (Figure 4) 43.Figure 3: The percentage of the cardiac circumference occupied by infarction in seven dogs after left anterior descending artery occlusion. A significant decrease of the infarcted area was found in both epicardial and endocardial regions during thoracic epidural anesthesia (TEA) modified from [44].Figure 4: Recovery of wall thickening fraction (WTF) from myocardial stunning in conscious dogs with and without thoracic epidural anesthesia (TEA). During the 48-h reperfusion period after a 10-min occlusion of the left anterior descending artery, dogs recovered significantly faster with TEA modified from [43].In humans, improvement in the myocardial oxygen supply by TEA may be related to the dynamic nature of approximately 75% of coronary stenoses 53,54, which can be modulated by pharmacologic or hemodynamic interventions 55. By inducing a high-level TEA (T1-T6) with bupivacaine, Blomberg et al. 47 were able to increase the luminal diameter of stenotic coronary arteries in 64% of patients, whereas no effects were seen on nonstenotic segments. Studies have suggested that beta-blockers cause a direct constriction of coronary arteries by unmasking the effect of postjunctional alpha-receptors 56,57. Because as nearly all patients in the study of Blomberg et al. 47 received beta-blocker-therapy, a decrease in the stimulation of alpha-adrenergic receptors may have increased blood flow through arterioles with diseased endothelium. Another indicator that increased blood flow is the main determinant in improving the ratio of oxygen supply and demand during TEA is the observation that in patients with unstable angina pectoris, high-level TEA reduced ST depression at a comparable workload during an exercise stress test 14. In patients with stable angina pectoris, TEA reduced ST depression during exercise 14,48, although the 15% higher ejection fraction with TEA could not be explained entirely by lower RPP 48. In addition, TEA has been used to treat anginal pain after multiple attempts to stop nitrate infusion have failed 14 and for long-term treatment of anginal pain 58. Further support that the beneficial effects of TEA are not confined to hemodynamic changes is provided by an experimental study by et al. coronary lead to ST segment and a concomitant decrease in which is under TEA. This beneficial effect was also when hemodynamic changes were by blood or Intramyocardial of adenosine and Intramyocardial use is by cardiac and the nervous system plays a role in that TEA should ventricular and but that it may cause In dogs, the of epinephrine to arrhythmia was significantly with TEA (Figure this effect was not with the of the is not an effect of local anesthetic and therefore represents an effect of sympathetic blockade by epidural This result agrees with an study in in which the of ventricular arrhythmias after coronary with and without TEA was The of ventricular in the first after of the left coronary artery was in the with in the TEA Studies on with of hemodynamic variables are a direct effect can be to TEA and is of epinephrine in the of of during anesthesia in dogs modified from TEA thoracic epidural by increases in and often occurs after major It has also been in the of unstable angina and myocardial infarction effects of epidural anesthesia on have been studies this used lumbar epidural anesthesia not TEA. The Anesthesia reported a significantly reduced rate of in patients undergoing lower who received epidural In patients with activity was after the with patients who received epidural anesthesia In patients undergoing major vascular surgery, et al. found in a patient after regional anesthesia in the anesthesia In the epidural was reduced effects of TEA can be caused by the systemic of the local which leads to to the reduction of stress response with epidural anesthesia and analgesia may function and the of in In addition, blood and is improved Lumbar or Thoracic An important is whether beneficial effects can be achieved by of TEA. Sympathetic blockade leads to effects on the vascular of sympathetic in to and of the has shown a of either or induced sympathetic activity during epidural anesthesia Epidural blockade of lumbar segments in an increased sympathetic activity in due to but TEA total of activity have an risk of cardiovascular depression and The most cardiovascular and arterial vasodilation, are usually with and as well as when due to the is often to treatment and the of Patients hypotension and with blood and cardiac contractility This results in arterial and mediated Because of the of the sympathetic blockade and vasodilation, this occurs more often with with TEA. In an experimental in the of for with blockade to the thoracic level induced a reduction of myocardial blood flow to a coronary artery The reduction in oxygen supply due to hypotension during is not followed by a concomitant reduction in demand This might be by an enhanced sympathetic in intact which has been demonstrated for and TEA in During TEA, the decrease in CBF to be by a decrease in myocardial oxygen demand and cardiac in MAP are not followed by wall during TEA but are during et al. found improved cardiac performance during exercise with TEA with left ventricular and regional wall were improved under TEA and were with ST segment In conclusion, TEA has more effects in the patient with coronary artery Epidural Anesthesia in TEA has several in myocardial anginal pain is improved, when the stress response to surgery is and the of myocardial and arrhythmias may be have been studies that on the effect of TEA in an should epidural anesthesia in the study by et al. in can be because of results further 1). patients undergoing or vascular surgery were The first received epidural and the received anesthesia The number of cardiovascular was significantly higher in the with anesthesia were in this more whereas all patients in the anesthesia myocardial in the anesthesia in the anesthesia 1: Studies the of Anesthesia or on level of epidural anesthesia or was not and the of anesthesia the postoperative pain therapy was or The study was with to and of surgery, and patients were not to concomitant The high of and high have on the of this The results by et al. were not in a study by et al. of patients undergoing The patients were in either a anesthesia or TEA in with coronary artery disease, hemodynamic and cardiovascular treatment were in both All patients received a thoracic epidural which was not used in the anesthesia was no difference between cardiovascular and pain was not or no the perioperative period can be on this The effects of epidural anesthesia during the postoperative period was investigated in a study by and patients from and undergoing major vascular surgery to the effects of anesthesia with analgesia or anesthesia with epidural anesthesia and Patients in the high lumbar or thoracic epidural The concomitant were comparable in both for a significantly higher rate of and myocardial infarction in the anesthesia The rates of and postoperative as well as the duration of the were significantly reduced in the anesthesia A study of the use of epidural and anesthesia anesthesia was by the in patients undergoing lower were at or differences were with to or However, the for was reduced in the epidural A more study by et al. found no significant difference in the effects of lumbar regional or anesthesia on perioperative cardiac morbidity and in patients undergoing peripheral vascular this study is a of the of this it is because it provided an The cardiac death rate with regional anesthesia to a anesthetic was significantly higher with that of patients undergoing regional or Recovery from epidural anesthesia is of clinical et al. reported patients who cardiac caused by coronary during recovery from epidural that this might be caused by between the and sympathetic nervous not the of investigation is clearly to the role of epidural analgesia especially when via the thoracic segments. TEA in Patients undergoing coronary artery have an increased risk of perioperative cardiac to reduce the perioperative risk have been the of several and a on the influence of TEA in patients undergoing TEA was with and in with anesthesia with Epidural from to segments. postoperative outcome, and adrenergic were with a and stability and lower heart rate in the reduced use of for the treatment of myocardial ischemia in the TEA (Figure patients who received TEA during and after and were This effect of TEA was first by et al. who were able to patients after patients were and pain was with analgesia of and cardiac function were changes in stress in patients, and found increase in and variability in epinephrine when anesthesia was with TEA during was higher during the period in the in the anesthesia During the first and postoperative lower epinephrine and were found in the TEA a, of cardiac in the postoperative period after coronary artery with anesthesia and anesthesia thoracic epidural anesthesia (TEA). b, of and taken from more the results of and and the effects of TEA as an to or in patients undergoing TEA was induced by followed by the were not able to test the of the due to with a from to stability in both TEA was with a reduced for or in both TEA In and an in the hemodynamic to surgery by inducing epidural blockade from to segments with of as an to a oxide hemodynamic stability and in patients in with for TEA with was found by et al. also postoperative function, and patients in the TEA were The of the local anesthetic was to higher in the studies of et al. and et al. with those of et al. and Blomberg et al. of a but not smaller of local anesthetic to be to or metabolic to surgery and to reduce perioperative morbidity have been the of a number of studies The response to surgery, and myocardial infarction leads to an increase in the of myocardial oxygen consumption which may to myocardial ischemia and infarction in patients with reduced coronary and demonstrated a decrease in the of during TEA. The related decrease in myocardial oxygen consumption may have beneficial effects under ischemic by epinephrine and is or under TEA. 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