Thoracic epidural anesthesia for treatment of angina

PRO AND CON P a u l G. Barash, M D Section Editor

THORACIC EPIDURAL ANESTHESIA FOR TREATMENT OF ANGINA Pro: The Anesthesiologist Should Provide Epidural Anesthesia in the Coronary Care Unit for Patients With Severe Angina Peter S. Staats, M D , a n d S u n i l J. Panchal, M D

PPER THORACIC epidural anesthesia (TEA) is a lowrisk techniqueI that can be performed on almost any patient with myocardial ischemia to improve analgesia and myocardial perfusion, decrease the incidence and severity of arrhythmias, and decrease the size of myocardial infarction. TEA is grossly underused and should be considered for patients with status angina as well as patients with end-stage multivessel disease not amenable to revascularization. Catheters should be placed by physicians with a knowledge of spinal anatomy, epidural analgesia, and cardiac pathophysiology. Although the risk/benefit ratio of placing and managing a patient with an epidural catheter for status angina needs to be considered, it is a very safe procedure in experienced hands.

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MAXIMIZING SUPPLY AND DEMAND

The goals of the physician caring for patients with status angina are to relieve pain and suffering, decrease the incidence of sudden death, and decrease adverse long-term sequelae (left ventricular [LV] dysfunction and infarction size). All of these can be achieved by improving the ratio of myocardial oxygen supply and demand. Many approaches have been used toward these ends. Medications have been used to vasodilate stenotic vessels or thin blood, thereby improving the supply side of the curve. Other medications have also been used to decrease inotropy and thus the myocardial oxygen demand (most commonly beta-blockers). In addition, percutaneous angioplasty and surgical revascularization are performed to improve the supply side of the curve. Although the value of attenuating sympathetic nervous system activity has been known for decades, there was a high associated mortality rate with surgical sympathectomy. With the advent of percutaneous angioplasty and coronary revascularization, surgical sympathectomy fell out of favor. However, recently, a number of reports have emphasized the importance of the sympathetic nervous system in chronic angina as well as the safety and efficacy of TEA in patients with status angina. ANGINA AND THE SYMPATHETIC NERVOUS SYSTEM: A VICIOUS CYCLE

Over the past 35 years, sympathetic nervous system activity has been shown to be detrimental in patients with myocardial ischemia, disturbing the capability to match blood flow (supply)

with demand, thus precipitating arrhythmias. Myocardial ischemia elicits a cardiac sympathetic reflex that increases catecholamine levels and (recorded) cardiac sympathetic neural discharge. There are several lines of evidence that this sympathetic activity leads to adverse consequences in patients with ischemia. First, 75% of arteriosclerotic coronary stenoses behave in a dynamic fashion, constricting intraluminal coronary artery diameter further with sympathetic stimulation by the isometric hand grip or cold pressor test. 2,3 Second, left sympathetic stimulation is known to cause a decrease in coronary blood flow distal to a left anterior descending (LAD) stenosis in patients with LV anterior wall dyskinesia and ST elevation. 4 Total blood flow is also known to be redistributed away from the endocardium to the epicardium, resulting in decreases in coronary blood flow and coronary diastolic pressure (during sympathetic nerve or stellate ganglion stimulation). Further evidence for the adverse consequences of sympathetic stimulation comes from the smaller infarct size noted after coronary occlusion in animals given labetelol over beta-blockers alone. Additionally, neurally decentralized dogs with left stellate ganglion stimulation had increased infarct size with beta-blockade, which was prevented by pretreatment with prazosin, all pointing to the importance of alpha-receptor activity in infarct size. s Although the alteration in perfusion pressure may occur because of direct stimulation of cardiac sympathetic fibers, sympathetic stimulation also affects platelet activity in diseased coronary segments, which further exacerbates the decrease in perfusion. This occurs by two general mechanisms. First, the majority of serotonin in the coronary vasculature is carried by platelets and is released early in the process of platelet aggregation or-dot formation. Then, with adrenergic stimula-

From the Departments of Anesthesiology and Critical Care Medicine and Oncology, Johns Hopkins University, Baltimore, MD. Address reprint requests to Peter S. Staats, MD, Director, Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, 600 N Wolfe St, Osler 304, Baltimore, MD 21287-5354. Copyright © 1997 by W.B. Saunders Company 1053-0770/97/1101-002353.00/0 Key words: epidural anesthesia, epidural analgesia, coronary artery disease, angina pectoris, coronary care unit

Journal of Cardiothoracic and Vascular Anesthesia, Vol 11, No 1 (February), 1997: pp 105-108

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tion, serotonin further precipitates coronary vasoconstriction. A second mechanism, known as Folts' phenomenon, involves the fact that adrenergic stimulation is known to exacerbate vasoconstriction. Thus, sympathetic activation by increased circulatory catecholamines triggers cyclic platelet accumulation in focal areas of disease in coronary circulation with resultant further decreased coronary blood flow. Finally, serotonin not only increases vasoconstriction but can theoretically increase the myocardial demand and subsequent ischemia. Serotonin, in concentrations less than that released by platelets, has been shown to cause an immediate hypertensive response, doubling the central aortic pressure for a few seconds in the dog model. Another concern in status angina is the development of arrhythmias with an increased myocardial oxygen demand. The ischemic heart is more sensitive to arrhythmias from catecholamines, and the sympathetic nervous system is capable of direct arrhythmogenic influence on ischemic myocardium independent of heart rate. 6 This is most likely caused by slowed conduction in ischemic myocardium from sympathetic stimulation, which allows reentrant phenomena to occur. Another adverse effect of sympathetic stimulation with infarction is the risk of increasing myocardial hypertrophy. Although the studies are not clear in humans, postinfarct myocardial hypertrophy in the rat occurs with increased sympathetic activity. This postinfarct myocardial hypertrophy can lead to increased myocardial work and, again, decreasing supply. Thus, there are multiple reasons to believe that an increase in sympathetic activity in patients with status angina could lead to a worse outcome. Likewise, sympathectomy in the patient with myocardial ischemia could prove very useful and result in better long-term outcomes.

Sympathectomyfor Angina The concept of sympathectomy for the control of angina is not new. The role of the sympathetic nervous system in control of circulation was first described in 1852 by Bernard and Sequard. 7 Stellectomy for angina was performed by Mayo in 1913 and Jonnesco in 1921 with up to 12 angina-free years. Reports of percutaneous alcohol neurolysis, thoracoscopic ganglionectomy, and open surgical sympathectomy demonstrated clear benefits, but surgical techniques in that era had operative mortality rates of 5% to 10% and thus fell out of favor with the advent of nitrates and coronary revascularization. Also, at that time, it was not recognized that the procedures directed at the sympathetic nervous system had benefits beyond pain relief. Stellate ganglion blocks and surgical stellectomy do, in fact, have various beneficial effects beyond the analgesic effect. Stellectomy attenuates the cyclical decreases in coronary artery blood flow in stenotic vessels caused by platelet aggregationdisaggregation in dogs and also leads to smaller new infarcts and lower mortality rates versus controls. Wiener and Cox s demonstrated that patients with bilateral stellate block before exercise electrocardiogram evaluation had no angina and decreased ST-segment depression versus bilateral sham injections. Cardiac denervation also attenuated the decrease in ventricular contractile force after coronary artery occlusion compared with controls (13% v 65%) with no cyanosis of myocardial tissue. 9

STAATS AND PANCHAL

Chronic denervation was more protective than acute denervation, as infarct size after LAD occlusion was 3.8% and 15%, respectively, but both were significant improvements over the results of control and sham-operated dogs (20.1% and 21%). l° This advantage is mostly caused by sympatholysis because sympathectomized dogs had 42% smaller infarcts after LAD occlusion than did control or sham-operated dogs. t l Also, there were no differences between the groups in regard to arterial pressure or heart rate, but sympathectomized dogs had 200% to 400% greater regional blood flow by labeled microsphere perfusion scan, indicating increased collateral flow. These findings are reflected in a publication of 24 unstable angina patients who underwent endoscopic thoracic sympathectomy, with a decrease in resting heart rate, decreased frequency of angina (10 were angina free), and no change in systolic blood pressure. 12 They also had increased exercise tolerance and lower ST-segment depression at maximum exercise, which is similar to Birkett's findings in patients after bilateral T1-T4 sympathetic ganglion resection. Prevention of severe arrhythmia has also been documented in animal models and in clinical trials. Dogs who had LAD ligation followed by either left stellectomy or no therapy (as controls) were subjected to acute circumflex coronary artery occlusion 1 month later. The stellectomy group had a lower incidence of ventricular fibrillation (33% v 65%), fewer arrhythmias among survivors, shorter QT intervals, and lower heart rates than the control group. Left stellate ganglion block or complete cardiac sympathectomy has been shown to prevent ventricular ectopy secondary to ischemia, resulting in slower heart rates and, therefore, less myocardial oxygen demand, t3 Lindgren performed open sympathectomy on 88 patients with severe angina with the following long-term results: ½ of patients became symptom free; ~ were significantly improved; and ½ were unchanged.14 White and several other investigators report good long-term results with stellectomy (1 to 11 years free of angina). 15 Bilateral neurolytic stellate block and sympathectomy for Prinzmetal's angina after poor response to coronary artery bypass graft (CABG) have been reported to have successful long-term results as well. The past decade has seen a large increase in the use of TEA as an alternate approach to achieving a beneficial sympathectomy in this patient population. TEA provides a sympathectomy without subjecting the patient to surgery. Davis et al compared TEA with lidocaine 1 hour after LAD occlusion versus controls given intramuscular lidocaine in dogs. The TEA group had lower heart rates and cardiac index, w iJh higher systemic vascular resistance and diastolic filling time (12.8%) and no change in the systemic vascular index (SVI). They also had a higher endocardial-to-epicardial regional myocardial blood flow ratio in the ischemic region (0.79 v 0.54), no change in nonischemic coronary vascular resistance, and lower coronary resistance for collateral flow in the ischemic zone (3.35 v 4.31) lnfarct size was significantly lower (16.7% v 30%) as was the arrhythmia score, without any difference in plasma or myocardial concentrations of lidocaine between groups? 6J7 In comparison with beta-blockade, TEA was shown to decrease left ventricular end-diastolic pressure (LVEDP) (opposite effect) and improve the o2 supply/demand ratio in rats with

PRO AND CON

existing maximum beta-blockade? 8 TEA has been shown to maintain a stable hemodynamic profile because thei'e is no change in SVI or stroke work index in healthy individuals or any change in mean arterial pressure, diastolic arterial pressure (DAP), coronary perfusion pressure (CPP), SVI, or peripheraJ vascular resistance index (PVRI) in unstable angina patients. ~9,2° TEA decreased heart rate by 7% to 10%, improved the 02 demand/supply balance, and improved myocardial performance, as the PCWP decreased by 42% with no change in stroke volume. 21 In patients receiving metoprolol, TEA did not demonstrate any difference in systolic arteria! Pressure (SAP), DAP, rate pressure product (RPP), globular regional ejection fraction versus controls at rest; with exercise, TEA increased globular ejection fraction while decreasing RPP. Global and regional left ventricular function was improved, and ST changes were decreased. 22 TEA causes a profound redistribution of myocardial blood flow to end0cardium, with the greatest increase in the most compromised hearts, which is not caused by a decrease in LVEDP. More important is the 20% to 25% decrease in coronary vascular resistance for collateral flow into the ischemic myocardium. Also, arteriography has shown TEA to significantly increase the diameter of stenotic segments without any change on nonstenotic segments or small-vesseI coronaries. Protection from arrhythmia is also evident, as ventricular refractoriness is prolonged by TEA in dogs, and the incidence of malignant ventricular arrhythmia was greatly reduced in rats. This was also observed in the series of studies by Blomberg, which also demonstrated the rapid effectiveness in unstable angina patients. Within 10 to 15 minutes, patients who failed maximal medical therapy had relief of angina, and 26/28 patients no longer required nitroglycerin within 3 hours. 23 Blomberg has also demonstrated a reduced incidence of angina and increased exercise tolerance in inoperable patients with refractory unstable angina who received TEA for long-term home self-treatment.

Spinal Cord Stimulation

Recently, spinal cord stimulation (SCS) has been used to improve blood flow in patients with peripheral vascular disease as well as patients with angina. Although there are very few studies available on this modality, it appears to be a promising therapeutic approach for chronic angina.2a This probably results from the sympathectomy effect of SCS. Research by anesthesiologists involved with epidural analgesia may find this to be a "long-term" solution for the management of chronic angina. Complications. Ultimately, the decision to pursue TEA for unstable angina will depend on the favorable risk/benefit ratio of this approach. Of concern is the risk of possible hematoma, infection, headache, neurologic damage, and adverse reaction to agents being administered. In the general population, Lund reviewed i50,000 patients Who received epidural anesthesia and found no instance of an epidural hematoma resulting in a neurologic deficit. Another series of 100,000 patients had only 5 patients with either a transient or permanent neurologic complication. Also, among 15,000 epidural blocks, there was only one reported epidural abscess, with its incidence being 0.2 to 1.9 per

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10.000 hospital admissions. Dawkins reported only 2 cases of permanent damage to the spinal cord and transient paralysis in one in more than 8.000 patients with TEA. and none was reported by Blomberg. Even chronic epidural catheterization had an infection incidence of 1 in 1,702 patient days without any requirement for surgical intervention. As for patients requiring anticoagulation, the risk of hematoma from epidural catheterization is also very low. Seven thousand patients with epidural or spinal anesthetics for vascular procedures with heparinization after needle insertion had no spinal hematoma. TEA has also been used safely in the perloperauve period for CABG. Horl0cker and Wedel have recommended that the epidural catheter is removed 4 to 6 hours after the last administration of heparin and that 1 hour passes before resuming anticoagulation. This is supported by results of neurologists performing lumbar puncture in anticoagulated patients. In the case of spinal epidural hematoma (SEH), a relationship to the catheter must not be assumed because SEH occurs spontaneously in patients on warfarin or heparin without trauma and is most frequently found in the thoracic spine.

The Anesthesiologist as Part o f an "'Acute Ischemia Team '"

Once it has been established that TEA is reasonable, the most experienced physician should be involved in placing and managing the epidural catheter in patients With status angina. Only the anesthesiologist experienced in neuraxial techniques and possessing an in-depth knowledge of cardiac pathophysiology should be performing thoracic epidural analgesia. Because there is certainly stress associated with placing an epidural catheter, which in theory could precipitate further spasm of the coronary vasculature, everything should be done to minimize this risk. This can be accomplished by medically stabilizing the patient with opioid analgesics and swiftly placing the catheter with minimal trauma. Moreover, the anesthesiologist should not tunction in a vacuum and should be part of an "acute ischemia care team" that includes a cardiologist and cardiac surgeon in decision making. Together the team can decide whether medical management, surgery, or TEA has the most favorable risk/ benefit ratio. Specific guidelines for implantation still need to be developed.

CONCLUSION

In conclusion, TEA is a safe and reliable method to achieVe a selective sympathectomy in order to produce beneficial physiologic changes i n the patient with myocardial ischemia. It is effective, can be delivered quickly, and may protect the patient from life-threatening arrhythmias and massive infarction wlth.out hemodynamic compromise. The level of stress in these patients should be minimized, and this procedure should 0nly be performed by anesthesiologists experienced in neuraxial techniques. Ideally, it should be instituted in ischemic patients who have failed medical management before anticoagulation. This is a simple and effective method to stabilize the ischemic patient and allow definitive therapy to be performed in a controlled manner, whether it be CABG, percutaneous transluminal coronary angioplasty, SCS, or long-term TEA.

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STAATS AND PANCHAL

REFERENCES

I. Blomberg S, Curelaru I, Emanuelsson H, et at: Thoracic epidural anesthesia in patients with unstable angina pectoris. Eur Heart J 10:437-444, 1989 2. Brown BG: Response of normal and diseased epicardial coronary arteries to vasoactive drugs: Quantitative arteriographic studies. Am J Cardiol 56:23E-29E, 1985 3. Gould KL: Dynamic coronary stenosis. Am J Cardio145:286-292, 1980 4. Uchida Y, Murao S: Sustained decrease in coronary blood flow in excitation of cardiac sensory fibers following sympathetic stimulation. Jpn Heart J 16:265-279, 1975 5. Flatley KA, DeFily DV, Thomas JX: Effects of cardiac sympathetic nerve stimulation during adrenergic blockade on infarct size in anesthetized dogs. J Cardiovasc Pharmacol 4:673-679, 1985 6. Euler DE, Nattel S, Spear JF, et al: Effect of sympathetic tone on ventricular an'hythmias during circumflex coronary occlusion. Am J Physiol 249:H1045-H1050, 1985 7. Drott C: The history of cervicothoracic sympathectomy. Eur J Surg 572:5- 7, 1994 (Suppl) 8. Wiener L, Cox JW: Influence of stellate ganglion block on angina pectoris and the postexercise electrocardiogram. Am J Med Sd 252:289-295, 1966 9. Thomas JX, Randall WC, Jones CE, et al: Effect of coronary occlusion on contractile force in the denervated heart. Fed Proc 36:1316, 1977 (abstr) 10. Jones CE, Devous MD, Thomas JX, et al: The effect of chronic cardiac denervation on infarct size following acute coronary occlusion. Am Heart J 95:738-746, 1978 11. Jones CE, Beck LY, DuPont E, et al: Effects of coronary ligation on the chronically sympathectomized dog ventricle. Am J Physiol 235:H429-H434, 1978 12. Wettervik C, Claes G, Drott C, et al: Endoscopic transthoracic sympathicotomy for severe angina. Lancet 345:97-98, 1995 13. Schwartz PJ, Stone HL: Left stellectomy in the prevention of ventricular fibrillation caused by acute myocardial ischemia in con-

scious dogs with anterior myocardial infarction. Circulation 62:12561265, 1980 14. Lindgren I: Angina pectoris: A clinical study with special reference to neurosurgical treatment. Thesis. Acta Med Scand 1950:1141. 15. White JC, Smithwick RH, Simeone FA: The autonomic nervous system. New York, Macmillan, 1952, pp 256-295 16. Davis RF, DeBoer LWV, Mar0ko PR: Thoracic epidural anesthesia reduces myocardial infai-ct size after coronary artery occlusion in dogs. Anesth Analg 65:711-717, 1986 17. Palumbo LT, Lulu DJ: Anterior transthoracic upper dorsal sympathectomy. Arch Surg 92:247-257, 1966 18. Blomberg S, Ricksten S-E: Effects of thoracic epidurai anaesthesia on central haemodynamics compared to cardiac beta adrenoceptor blockade in conscious rats with acute myocardial infarction. Acta Anaesthesiol Scand 34i 1-7, 1990 19. Liem TH, Moll JE, Booij LHDH: Thoracic epidural analgesia in a patient with bilateral phaeochromocytoma undergoing coronary artery bypass grafting. Anaesthesia 46:654-658, 1991 20. Otton PE, Wilson EJ: The cardiocirculatory effects of upper thoracic epidural analgesia. Can Anaes Soc J 13:541-549, 1966 21. Blomberg S, Emanuelsson H, Ricksten S-E: Thoracic epidural anesthesia and central hemodynamics in patients with unstable angina pectoris. Anesth Analg 69:558-562, 1989 22. K0ck M, Blomberg S, Emanuelsson H, et al: Thoracic epidural anesthesia improves global and regional left ventricular function during stress-induced myocardial ischemia in patients with coronary artery disease. Anesth Analg 71:625-630, 1990 23. Blomberg S, Curelaru I, Emannelsson H, et al: Thoracic epidural anaesthesia in patients with unstable angina pectoris. Eur Heart J 10:437-444, 1989 24. Chandler M J, Brennan TJ, Garrison DW, et al: A mechanism of cardiac pain suppression by spinal cord stimulation: implications for patients with angina pectoris. Eur Heart 14:95-103, 1993