Pro: Regional anesthesia is better than general anesthesia for lower extremity revascularization

PRO AND CON J, Earl Wynands, MD, Editor

REGIONAL ANESTHESIA IS BETTER THAN GENERAL ANESTHESIA FOR LOWER EXTREMITY REVASCULARIZATION Pro: Regional

Anesthesia

is Better Than General Revascularization

Anesthesia

for Lower Extremity

Kenneth J. Tuman, MD, and Anthony D. Ivankovich, MD

T

HE IMPORTANCE OF choice of anesthesia for lower extremity revascularization has been debated for many years, and many clinicians have developed strong convictions that certain anesthetic techniques are preferable for these patients. In the past, there were often little objective data to support such beliefs. Objective measures of outcome in patients undergoing lower extremity revascularization are of great significance because of the high incidence of morbidity after such procedures as well as the relationship of that morbidity to pathophysiologic changes in the perioperative period. These considerations are essential to understanding the advantages of regional anesthesia compared to general anesthesia for patients undergoing lower extremity revascularization. It is apparent that most serious morbidity actually occurs in the hours and days following noncardiac surgery and this temporal discontinuity with the stressful intraoperative period has prompted new focus on the immediate postoperative period. The termination of anesthesia and surgery, with emergence and transition into the postoperative period, is associated with continued activation of the sympathetic nervous system. Control of the hyperadrenergic state and the postoperative stress response has implications for metabolism, the immune response, coagulation and the cardiovascular system and may have an important impact on outcome. The presence of pain, anxiety, an endotracheal tube and physiologic derangements such as hypoxemia, hypercarbia, hypothermia, as well as intravascular volume overload or depletion with anemia, all serve as potent stimulants to increase serum catecholamine levels, accelerate coagulability, and potentially contribute to a number of postoperative cardiovascular complications. Both epinephrine and norepinephrine concentrations increase three to six times normal during major vascular surgery.1 Postopera-

From the Department ofAnesthesiology, Rush-Presbyterian-St Luke S Medical Center, Chicago, IL. Address reprint requests to Kenneth J. Tuman, MD, Department of Anesthesiology, Rush-Presbyterian-St Luke’s Medical Center, 1653 W Congress Parkway, Chicago, IL 60612. Copyright o 1994 by W. B. Saunders Company 1053-0770194/0801-0032$03.00/0 Key words: vascular surgery, regional anesthesia 114

tively, plasma epinephrine levels return to normal more rapidly than do norepinephrine levels, which can remain elevated for several days, probably because of afferent nerve traffic from the site of injury as well as central sensitization.*s3 Considerable interest has therefore developed in the use of epidural opioids or dilute solutions of local anesthetic to blunt the perioperative stress response. How effective are these methods for controlling the hyperadrenergic response and reducing perioperative cardiovascular morbidity? Attenuation of the norepinephrine response after major vascular surgery has been demonstrated in patients receiving epidural morphine for postoperative analgesia.1,J In addition, the typical postoperative increase in heart rate is reduced threefold when epidural anesthesia and analgesia (EAA) is used after major vascular surgery and there is an analogous reduction in the increase in the rate-pressureproduct with EAA.5 Though the absolute clinical significance of the reduction in heart rate is unclear, recent data suggest that this is a meaningful difference because patients with postoperative ischemia after peripheral vascular surgery who suffer adverse outcomes have higher overall heart rates than patients with postoperative ischemia who do not suffer adverse outcomes.6 The occurrence of postoperative tachycardia may not be causally related to ischemia but it appears to play a role in the genesis of cardiac events in high-risk vascular patients. BENEFITS OF EAA: OBJECTIVE

EVIDENCE

Reiz et al were some of the first to report outcome data with different anesthetic and analgesic regimens in highrisk patients undergoing emergency major vascular surgery in the face of recent myocardial infarctions.’ There was a lower incidence of myocardial ischemia and ventricular dysfunction and a lower myocardial reinfarction rate when patients were randomized to receive EAA. Subsequently, Yeager et al8 demonstrated that high-risk patients had far fewer cardiovascular, infectious, and overall complications when they received EAA compared to a general anesthesia group that received 60 pg/kg of fentany18 A subset of patients in the latter study underwent major vascular surgery and also demonstrated similar beneficial effects of EAA. Though this study was essentially the first controlled

Journalof Cardiothoracic and VascularAnesthesia,

Vol8, No 1 (February), 1994: pp 114-l17

PRO AND CON

randomized trial to show beneficial outcome effects of anesthetic management in high-risk noncardiac surgery, it has remained controversial and widespread application to clinical practice has been limited, probably because of the heterogeneity and relatively small size of the study population as well as the comparison of EAA with a high-dose opioid “cardiac style” anesthetic. A randomized trial of general anesthesia combined with EAA versus general anesthesia alone for aortobifemoral or lower extremity vascular surgery at the authors’ institution validated Yeager’s findings of reduced postoperative cardiovascular morbidity with EA4.9 In fact, CHF and non-use of EAA were the only two independent predictors of cardiovascular complications in this study. Besides reducing levels of circulating catecholamines and other mediators of the postoperative hyperadrenergic and “stress” response,4 EAA may alter cardiovascular outcome by additional positive interactions with the cardiovascular system. Thoracic epidural anesthesia has been associated with improved global and regional left ventricular function during stress-induced myocardial ischemia in patients with coronary artery disease. lo The exact mechanism for these beneficial effects may not only involve reduction of circulating catecholamines, but may be related to altered myocardial loading conditions. Lumbar epidural anesthesia is associated with a marked improvement in baseline regional wall motion abnormalities, although intravascular fluid loading somewhat attenuates this effect,” indicating that alteration in load conditions may be one influence of EAA on the myocardium. Animal studies indicate that epidural application of local anesthetic may also be associated with beneficial effects on the distribution of intramyocardial blood flow, with reduction in both epicardial and endocardial infarct size after acute coronary artery occlusion.‘* Thus, there may be multiple ways in which EA4 may modulate or attenuate adverse cardiovascular events. In addition, continuous EAA with dilute solutions of local anesthetic and opioid has been associated with less early vascular graft thrombosis as well as fewer overall thrombotic complications, defined as thrombosis of a vascular graft, deep leg vein, or coronary artery.9 Despite the smaller size of the subpopulation undergoing only infrainguinal revascularization in the study of Tuman et a1,9 a statistically and clinically meaningful difference was still achieved when comparing the incidence of vascular graft failure in the general anesthesia group (6/20) with the EAA group (1/2S).13 These findings were present with no evidence of technical problems such as intimal flaps, other anastomotic defects, or inadequate outflow as assessed by independent observers using arteriograms performed immediately after completion of operation.13 The PIRAT (Perioperative Ischemia Randomized Anesthesia Trial) study group has also intensively examined the question of whether perioperative morbidity is modifiable in high-risk vascular surgical patients by the choice of either epidural or general anesthesia.14 Patients undergoing lower extremity revascularization were randomized to receive EAA or general anesthesia with intravenous patient controlled analgesia (PCA) for the first 24 hours postopera-

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tively. Both groups received intermittent on-demand opioid analgesia thereafter. In the PIRAT study, EAA was associated with lower catecholamine levels, especially in the transition from the end of the procedure until the measurements ended 18 hours postoperatively. The PIRAT study protocol included very strict control of blood pressure and heart rate during the intraoperative and immediate postoperative period and this alone may explain the lack of any significant difference in the incidence of myocardial ischemia between the anesthesia groups intraoperatively or on the first postoperative day. However, when either the PCA or the epidural analgesia (with opioid alone) was discontinued, ischemia increased from about 17% to about 30% of patients regardless of anesthestic group. The incidence of vascular graft complications (regrafting or embolectomy) during the hospital stay was also far less in the EAA group (2/49) than the general anesthesia group (ll/Sl) and the time necessary for regrafting, thrombectomy, or amputation was also shorter after general anesthesia than after epidural anesthesia in the PIRAT study. The pattern of reoperations for limb ischemia was temporally related to the administration of anesthesia and different between epidural and general anesthesia groups for the first few days after surgery, followed by similar reoperation rates thereafter. This is the expected pattern if the choice of anesthesia affected the outcome, because anesthetic effects on graft flow and coagulability would be greatest immediately after surgery and diminish over time. It is worth noting that the overall incidence of in-hospital reoperation rate for graft failure in the Tuman et al study9 (16%), as well as the PIRAT study14 (13%), are well within the usual range for lower extremity revascularreported in the literature 15-17 ization procedures (10% to 21%). Although a large number of surgical and patient variables (such as underlying vascular anatomy, type of material used for the vascular conduit, specific reconstructive techniques, distal extent of the revascularization, intraoperative methods to assess the adequacy of reconstruction, etc) influence outcome after peripheral vascular reconstruction, there is sufficient evidence that epidural anesthesia with transition to postoperative epidural analgesia has a significant effect on outcome in this high-risk population. Even considering patients who require synthetic conduits because of lack of usable vein, the incidence of acute vascular graft failure is much lower after peripheral revascularization with epidural anesthesia and analgesia than after general anesthesia.” A common denominator of the anesthesia outcome studies noted above is the postoperative neuraxial application of opioids with or without dilute solutions of local anesthetics. Failure to consistently continue epidural analgesia at least into the immediate postoperative period is a common flaw of other studies, which have not found salutary effects of epidural techniques in such high-risk patients.‘*J9 The use of epidural anesthesia intraoperatively with a transition to postoperative epidural analgesia should improve graft flow in the immediate postoperative period. A reduction in limb vascular resistance and augmented blood flow through newly grafted vessels occurs with epidural anesthesia in patients with atherosclerotic

TUMAN

116

vascular disease2” and may be an important determinant of the success of revascularization procedures in patients with severe vascular disease. Although many factors are involved, in general it would seem that the lower the graft flow, the greater the likelihood that the vascular graft will fail. Coagulation status may also be an important mediator of postoperative cardiovascular morbidity. Several lines of evidence strongly suggest that alterations in coagulation could be important in the development of cardiovascular complications in patients with significant arterial vascular disease. Acceleration of the coagulation state postoperatively has been demonstrated by multiple authors and in general this is characterized by increases in fibrinogen with declines in coagulation inhibitors, reduced fibrinolytic activity, and a hypercoagulable tendency that may be associated with cardiovascular morbidity.21 The PIRAT study demonstrated a strong association of elevated plasminogen activator inhibitor levels and impaired fibrinolysis with the occurrence of postoperative thrombotic events.22 A similar association of postoperative thrombotic complications with thromboelastographically detected augmentation of coagulation activity has been demonstrated? Interestingly, EAA has been associated with attenuation of this hypercoagulable response after lower extremity vascular surgery in two investigations,9,22 consistent with earlier work demonstrating less inhibition of fibrinolysi9 and smaller increases in coagulation factors with regional anesthesia than with general anesthesia.24 In the PIRAT study, plasminogen activator inhibitor levels did not rise in patients receiving EAA whereas they did with PCA.22 In the Tuman et al study, postoperative clot formation rate was reduced in vascular surgery patients receiving EAA.’ The evidence is mounting to strongly suggest a relationship between accelerated coagulation and the development of perioperative complications in patients with significant atherosclerotic vascular disease undergoing lower extremity revascularization, and that EAA is strongly associated with improved postoperative coagulation status. OUTCOME

AND EAA: INFLUENCE OF OTHER INTERVENTIONS

The importance of applying extraordinary care to the interpretation of clinical outcome studies cannot be overemphasized. Most clinicians are not surprised that healthy patients undergoing simple operative procedures such as cesarean section or knee surgery do not manifest outcome differences between EAA and other techniques when small numbers of patients are studied .25,26It is also not surprising that common features of those studies that have demonstrated beneficial effects of EA.4 are the high-risk nature of the patient population and the greater degree of perioperative stress to which patients are exposed. However, even within “high-risk” patient populations undergoing major operative procedures, significant heterogeneity exists in patient characteristics and perioperative surgical and medical management modalities. If surgical and patient variables or nonanesthetic management modalities permit reduction in morbidity to very low levels, it may be impossible to demonstrate any significant impact of anes-

AND IVANKOVICH

thetic management on morbidity after peripheral vascular surgery, even with large numbers of patients. Recent studies serve as excellent paradigms of this phenomenon. The PIRAT study was unable to confirm any significant difference in cardiac outcomes (perioperative death, nonfatal myocardial infarction, unstable angina, or myocardial ischemia) between anesthetic groups.14 This is likely related to the conservative vital sign limits used in this trial (especially the use of 85 beatsimin as the upper limit of heart rate) as well as the exclusion of similar patients undergoing more stressful operative procedures such as aortic surgery. These study characteristics increase the homogeneity of the study population, but also probably contribute to a low incidence of major cardiac morbidity, making it more difficult to demonstrate a difference in cardiac morbidity attributable to the type of anesthesia compared to the situation where such strict blood pressure and heart rate management is not used or when aortic surgical procedures are not excluded.8,9 Indeed, the remarkably low overall incidence of graft occlusion (1.6%) and low frequency of MI (4.4%) reported in the largest randomized trial of general versus regional anesthesia for lower extremity revascularization in a population of primarily diabetic patients is very likely related to the medical interventions made possible by careful, continuous monitoring with routine pulmonary artery catheterization, invasive blood pressure monitoring, and ICU care for 48 to 72 hours after surgery in every patient. l9 Control of blood pressure, heart rate, cardiac output, and vascular resistance with a variety of nonanesthetic interventions that attenuate the cardiovascular effects of perioperative sympathetic hyperactivity has been shown to impact positively on the outcome after peripheral vascular surgery. 27 There may be substantial physiologic parallels between the beneficial effects of EAA and the physiologic and pharmacologic interventions directed and initiated by collection of physiologic data obtained from such intensive monitoring. Although this is currently only a hypothesis, it is curiously consistent with the results of Berlauk et ak2’ which indicate that such intensive perioperative monitoring with optimization of systemic blood flow parameters is associated with a rate of graft occlusion (2.2%) after lower extremity vascular surgery, which was markedly reduced and very similar to that reported by Bode et al,” who also routinely used extensive perioperative monitoring after lower extremity vascular surgery. Avoidance of the depression of cardiac output seen with general anesthesia (as well as with postoperative mechanical ventilation, which is more likely after general than regional anesthesia) either by using regional anesthesia or routine pulmonary artery catheter monitoring to allow optimization of systemic blood flow, may contribute to a reduced incidence of graft failure. If intensive medical management or other nonanesthetic interventions markedly reduce the incidence of perioperative vascular and cardiac complications, the beneficial effects of EAA will not be manifest even if large numbers of patients are studied.iy It will be critical to determine whether intensive medical management before, during, and after peripheral vascular surgery in high-risk patients can achieve the same beneficial effects on outcome as the continuation of central neuraxial

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blockade into the recovery phase, because these data will be vital to future cost-effectiveness analyses that will necessitate balancing costs and benefits of such intensive hemodynamic and other monitoring or other interventions with costs and benefits of EAA. In this regard, it is noteworthy that the use of EAA as outlined by Yeager et al8 and Tuman et al is associated with reduced ICU stay and affiliated costs, in contrast to an alternative approach involving the use of prolonged intensive management as applied in the Bode et alI9 and Berlauk et alz7 studies. CONCLUSIONS

As competition for health care funds becomes progressively more intense, it is imperative for anesthesiologists to objectively examine the current understanding of whether

certain types of anesthetic techniques such as epidural anesthesia and analgesia in high-risk patients undergoing lower extremity revascularization can reduce the incidence of postoperative morbidity, which prolongs ICU stay as well as hospitalization or otherwise increase both direct and indirect costs. Though it is possible and even likely that other perioperative interventions unrelated to choice of anesthetic can also positively impact outcome after lower extremity revascularization, the outcome studies to date have generated solid basis for epidural techniques as the preferential choice for anesthesia and analgesia in these patients. Epidural anesthesia is not a magic bullet, but it is clearly the anesthetic technique with the greatest potential for reducing morbidity after lower extremity revascularization.

REFERENCES 1. Breslow MJ, Jordan DA, Christopherson R, et al: Epidural morphine decreases postoperative hypertension by attenuating sympathetic nervous system hyperactivity. JAMA 261:3.577-3581, 1989 2. Woolf CJ, Chong NS: Preemptive analgesia-treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 77:362-379, 1993 3. Brown DL, Mackey DC: Management of postoperative pain: Influence of anesthetic and analgesic choice. Mayo Clin Proc 68176%777,1993 4. Kataja J: Thoracolumbar epidural anesthesia and isoflurane to prevent hypertension and tachycardia in patients undergoing abdominal aortic surgery. Eur J Anaesthesiol8:427-436,199l 5. Diebel LN, Lange MP, Schneider F, et al: Cardiopulmonary complications after major surgery: A role for epidural analgesia? Surgery 102:660-666, 1987 6. Raby KE, Barry J, Creager MA, Cook EF, Weisberg MC, Goldman L. Detection and significance of intraoperative and postoperative myocardial ischemia in peripheral vascular surgery. JAMA 268:222-227,1992 7. Reiz S, Balfors E, Sorenson MB, et al: Coronary hemodynamic effects of general anesthesia and surgery: Modification by epidural analgesia in patients with ischemic heart disease. Reg Anesth 7:S8-S20,1982 8. Yeager M, Glass DD, Neff RK, Brinck-Johnson T: Epidural anesthesia and analgesia in high risk surgical patients. Anesthesiology 66:729-735, 1987 9. Tuman KJ, McCarthy RJ, March RJ, et al: Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 73:696-704,199l 10. Kock 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 71:62.5-630,199O 11. Baron J-F, Coriat P, Mundler 0, et al: Left ventricular global and regional function during lumbar epidural anesthesia in patients with and without angina pectoris: Influence of volume loading. Anesthesiology 66:621-627,1987 12. Davis RF, DeBoer LWV, Maroko PR: Thoracic epidural anesthesia reduces myocardial infarct size after coronary artery occlusion in dogs. Anesth Analg 65:711-717, 1986 13. Tuman KJ, McCarthy RJ, Ivankovich AD: Epidural anesthesia and analgesia in vascular surgery. Anesth Analg 75:465-467, 1992 14. Christopherson R, Beattie C, Frank SM, et al: Perioperative morbidity in patients randomized to epidural or general anesthesia

for lower extremity vascular surgery. Anesthesiology 79:422-434, 1993 15. Bandyk DF, Cato RF, Towne JB: A low flow velocity predicts failure of femoropopliteal and femorotibial bypass grafts. Surgery 98:799-807,1985 16. Hertzer NR, Avellone JC, Farrell CJ, et al: The risk of vascular surgery in a metropolitan community. J Vast Surg 1:13-21, 1984 17. Rhodes RS, Krasniak CL, Jones PK: Factors affecting length of hospital stay for femoropopliteal bypass: Implications of the DRGs. N Engl J Med 314:153-157,1986 18. Baron J-F, Bertrand M, Barre E, et al: Combined epidural and general anesthesia versus general anesthesia for abdominal aortic surgery. Anesthesiology 75:611-618,199l 19. Bode RH, Lewis KP, Pierce ET, et al: Graft occlusion after peripheral vascular surgery with general vs regional anesthesia (abstract). Proceedings of the Society of Cardiovascular Anesthesia Annual Meeting, San Diego, CA, April 1993 20. Cousins MJ, Wright CJ: Graft, muscle, skin blood flow after epidural block in vascular surgical procedures. Surg Gynecol Obstet 13359-65, 1971 21. Rosenfeld BA: Perioperative hemostatic changes and coronary ischemic syndromes, in Beattie C, Fleisher LA (eds): International Anesthesiology Clinics, ~0130. Boston, MA, Little, Brown & Company, 1992, pp 131-154 22. Rosenfeld BA, Beattie C, Christopherson R, et al: The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Anesthesiology 79:435-443,1993 23. Modig J, Borg T, Bagge L, Saldeen T: Role of extradural and of general anesthesia in fibrinolysis and coagulation after total hip replacement. Br J Anaesth 55:625-629,1983 24. Bredbacka S, Blomback M, Hagnevik K, et al: Pre- and postoperative changes in coagulation and fibrinolytic variables during abdominal hysterectomy under epidural or general anaesthesia. Acta Anaesthesiol Stand 30:204-210, 1986 25. Ellis DJ, Millar WL, Reisner IS: A randomized doubleblind comparison of epidural versus intravenous fentanyl infusion for analgesia after cesarean section. Anresthesiology 72:981-986, 1990 26. Loper KA, Ready LB, Downey M, et al: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg 70:72-75,199O 27. Berlauk J, Abrams JH, Gilmour IJ, et al: Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. Ann Surg 214:289-297,199l