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Catastrophic Outcomes of Noncardiac Surgery Soon After Coronary Stenting Kaluza GL, Joseph J, Lee JR, Raizner ME, Raizner AE, J Am Coll Cardiol 2000; 35:1288-94
Reviewer: KW Tim Park, MD
Background: Patients with cardiac problems who present for a high-risk noncardiac operations such as vascular surgery are often referred for preoperative cardiac work-up and, if the workup is positive for significant coronary artery disease (CAD), must be triaged to either medical optimization or surgical/interventional revascularization. Studies by Eagle et al. (Circulation 1997; 96:1882-7) have shown that prior surgical revascularization (CABG) is associated with a lower myocardial infarction (MI) and death rate in a subsequent abdominal, vascular, thoracic, and head and neck operations. Similarly, patients revascularized by percutaneous transluminal coronary angioplasty (PTCA) > 90 days before noncardiac operations have half the risk of adverse cardiac outcome as nonrevascularized CAD patients, though twice the risk of healthy controls (Posner KL et al. Anesth Analg 1999; 89:553-60). Interestingly, in this latter study, patients revascularized by PTCA < 90 days before noncardiac operations had no reduction in the risk of adverse cardiac outcome compared to nonrevascularized CAD patients. In the present study, the authors examined specifically if patients revascularized by PTCA with stenting < 6 weeks before noncardiac operations have a reduction in cardiac morbidity and mortality. Methods: Forty consecutive patients who underwent coronary stenting < 6 weeks before a noncardiac operation under general anesthesia at a single hospital were identified. Their records were examined retrospectively for adverse clinical events such as stent thrombosis, MI, bleeding complications, and death. Each patient's antiplatelet therapy during the perioperative period was noted. Results: The interval between coronary stenting and surgery ranged from 1 _ 39 days with an average of 13 days. Of the 40 operations, 26 were major vascular operations. Most patients had antiplatelet therapy (ticlopidine and aspirin) discontinued 0 _ 1 day before operation and restarted 0 _ 1 day after operation. Of the 40, 7 suffered MI, of which 6 were fatal. In two patients, stent thrombosis was confirmed angiographically. In 4 others, the stented artery subtended the area of infarction. The remaining patient had multiple stents for 3-vessel disease and suffered sudden death after chest pain. So in all 7, stent thrombosis was the likely cause of the MI. Another set of seven patients had bleeding complications. Two of the seven died of bleeding complications; in these patients, antiplatelet therapy had been continued perioperatively. All 8 patients who died underwent operations < 2 weeks after coronary stenting and represented 32 % (8/25) of all those who had operations < 2 weeks after coronary stenting. Discussion/Comments: Intracoronary stents have been advocated to improve the outcome of PTCA by reducing the need for emergent CABG and the rate of subsequent restenosis. In many centers, the stents are now used in more than 50 % of all PTCA procedures (Topol EJ & Serruys PW. Circulation 1998; 98:1802-20). Recent technological advances in stenting and antiplatelet regimens have reduced the 30-day stent occlusion rate to as low as 0.5 % (Leon MB et al. N Engl J Med 1998; 339:1665-71). Typically, ticlopidine and aspirin were started 3 _ 5 days before PTCA with stenting and continued for 14 _ 30 days, depending on the risk of stent thrombosis. Major operations may be associated with activation of the procoagulant system and the risk of stent occlusion may be increased by surgical stresses; what may be an adequate antiplatelet regimen in the nonsurgical period may not prove adequate during the perioperative period. Thus, patients requiring major noncardiac operations during the early post-stenting period pose a major dilemma, as discontinuation of antiplatelet therapy increases the risk of stent thrombosis and MI while continuing therapy, or addition of other anticoagulants such as heparin, increases the risk of major bleeding complications. The present study confirmed this suspicion and questioned the wisdom of noncardiac operations within the 14 - 30 day period of antiplatelet therapy after coronary stenting, especially if the operation is elective. If a patient is to be triaged to interventional revascularization for a preoperative workup positive for CAD, it should be ascertained that the combined morbidity and mortality of the intervention and subsequent noncardiac operation would be less than that of the noncardiac operation without the intervention. A prerequisite for this condition would be that those who survive the proposed interventional revascularization are able to undergo noncardiac surgery with reduced mortality and morbidity. In the case of revascularization by coronary stenting, the available data indicated that cardiac morbidity and mortality may actually increase if the noncardiac operation was performed within 14 _ 30 days of the stenting. A recent case report described a patient who had a cardiac arrest after nephrectomy 32 days after coronary stenting and required an emergent PTCA to reopen the thrombosed stent (Anesthesiology 2001; 94:367-8). As this case report illustrated, the exact duration one should wait after stenting before undergoing surgery may be longer than 30 days and possibly longer. In case of revascularization by PTCA without stenting, the purported benefits are not obvious, either. Posner et al.'s study (Anesth Analg 1999; 89:553-60) showed that patients revascularized by PTCA < 90 days before noncardiac operations might not be different from nonrevascularized controls in terms of perioperative cardiac outcome. The advantage of PTCA was demonstrated only if the interval from PTCA to surgery was > 90 days. If we factor in the morbidity and mortality of PTCA itself, it may be difficult to recommend PTCA for elective revascularization before major noncardiac operations. In fairness, Gottlieb et al. (J Cardiothor Vasc Anesth 1998; 12:501-6) reported that patients who undergo PTCA could then have vascular operations with an acceptably low incidence of cardiac morbidity, but in their study, there was no comparison to control cohorts. Prior CABG has been shown to be associated with a reduced mortality and MI rate after high-risk noncardiac surgery (Eagle KA et al. Circulation 1997; 96:1882-7). The reduction was especially significant in patients with more advanced CAD involving 2 or more vessels and the benefit appeared to be maintained for at least 6 years. What was not clarified in the study was whether the benefit was demonstrated in the immediate post-CABG period, say the first 30 days after CABG, or whether one needed to wait a certain period before undergoing another (noncardiac) operation. We will need to await future studies to answer this question. Use of the internal mammary artery graft and in-hospital mortality and other adverse outcomes associated with coronary artery bypass surgery. Leavitt BJ, O'Connor GT, Olmstead EM, Morton JR, Maloney CT, Dacey LJ, Hernandez F, Lahey SJ. Circulation 2001; 103: 507-512.
Reviewer: Mark A. Chaney, MD
Abstract: The evidence is clear that patients having coronary artery bypass grafting (CABG) with an internal mammary artery (IMA) have improved long-term survival. The short-term protective effects of an IMA graft, however, are somewhat controversial. Previous studies suggesting a short-term protective effect have been confounded by multiple other risk factors and the fact that older and sicker patients are less likely to receive an IMA graft. This study examined the independent effect of IMA grafts on in-hospital mortality while adjusting for patient and disease factors. These investigators studied use of the left IMA (LIMA) in 21,873 consecutive, isolated, first-time CABG procedures from 1992-1999. Eighty-seven percent of these patients received a LIMA graft, and which found to be protective across all major patient and disease subgroups. After adjustment for all major risk factors, LIMA use was associated with a significantly decreased risk of mortality (p<0.001). Rates of cerebrovascular accident, return to cardiopulmonary bypass, return to the operating room for bleeding, and mediastinitis or sternal dehiscence requiring surgery were also less in the LIMA group, although not significantly so. The investigators conclude that their data suggest that in addition to its well-documented patency and long-term beneficial effect, LIMA grafting has a strong protective effect on perioperative mortality. Comments: Since the introduction of the IMA as a conduit for CABG 30 years ago, numerous investigators have documented improved long-term patency and survival with IMA use when compared to venous conduits. Only recently have investigators studied the short-term effects of IMA use. These studies have suggested that short-term benefits exist yet questions have remained, mainly because of widespread regional differences in IMA use. This study was performed by the Northern New England Cardiovascular Disease Study Group, a voluntary research consortium from six medical centers in New England (34 cardiothoracic surgeons participated in the study). The investigators prospectively collected many perioperative variables in order to calculate adjusted odds ratios and generate summary predicted risk variables from multivariate statistical models and therefore examine the effect of LIMA grafts on in-hospital mortality while adjusting for patient and disease factors. They found that LIMA graft use was associated with a significantly decreased risk of in-hospital mortality and was protective across all major patient subgroups. Several previous observational studies have suggested this finding yet these studies were tainted by patient selection bias (patients receiving a LIMA were not as sick or as high-risk as those not receiving a LIMA). Thus, this investigation is important in that LIMA use was protective in every patient subgroup analyzed (patient selection bias eliminated). The authors hypothesize that biologic differences (physical and biochemical) between artery and vein grafts leading to improved patency and increased flow likely account for the protective benefits of LIMA grafts when compared to saphenous vein grafts. When compared to vein grafts, arterial grafts have no valves, fewer endothelial fenestrations, greater resistance to trauma, higher flow reserve, higher nitric oxide and prostacyclin production, as well as other biologic benefits. Furthermore, these investigators did not find that LIMA use was associated with a higher incidence of mediastinitis, sternal dehiscence, nor postoperative bleeding, all being feared complications of LIMA harvest. An accompanying editorial by Lawrence H. Cohn, M.D. (Harvard Medical School), puts this investigation into historical perspective. Dr. Cohn feels that this investigation by Leavitt, et al. is important in that it has been performed in the "modern" era (1990's) and it refutes many long-held beliefs by surgeons that the IMA should be avoided in certain clinical situations (left ventricular hypertrophy, severe left ventricular dysfunction, emergency operation, chronic obstructive pulmonary disease, advanced age, etc.). Dr. Cohn also properly notes that the multi-institutional nature of this large study is a strong, positive factor supporting the data. Thus, this investigation supports an even wider use of the IMA graft, even in difficult clinical situations (including emergencies, left ventricular dysfunction, elderly patients, etc.), and supports the continued trend toward total arterial revascularization.
Prevention of Radiographic-Contrast-Agent-Induced Reduction in Renal Function by Acetylcysteine. Tepel M, Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. N Engl J Med 2000;343:180-4
Reviewers: Kevin J. Cross and Albert
T. Cheung, MD
Introduction: Radiographic contrast agent-induced nephropathy is an important concern in patients undergoing cardiac operations and endovascular stent repair of aortic aneurysms. Postoperative renal dysfunction leads to increased morbidity and mortality. Coronary angiography in preparation for CABG requires 70-80 ml of radiographic contrast agent and left ventriculography requires an additional 45 ml. Intraoperative angiography for endovascular stent repair of aortic aneurysms require between 120 ml and 250 ml of radiographic contrast agent. To date, the only proven preventive measure and treatment strategy has been hydration. Agents such as furosemide, mannitol, calcium channel antagonists, theophylline, atrial naturetic peptide, and dopamine have failed to demonstrate any additional benefit. It is believed that contrast damages the kidneys by acutely changing renal hemodynamics and it exerting a direct toxic effect on renal tubular epithelial cells. Increased lipid peroxidation is believed to be an important factor leading to renal cell injury. Although contrast-induced nephropathy can occur in any patient, it is most common in patients with pre-existing chronic renal failure or diabetic nephropathy. Acetylcysteine (Mucomyst, Mucosil) was tested for renal protection because recent studies suggested that acetylcysteine caused vasodilatation, blocked the expression of vascular-cell adhesion molecule 1, and prevented the activation of nuclear factor-kB. These actions may rectify the hemodynamic changes produced by the contrast dye and inhibit the inflammatory processes thereby decreasing lipid peroxidation and its ill-effects on tubular cells. Method: In this prospective randomized study, 83 patients with chronic renal failure, defined by serum creatinine >1.2 mg/dl were treated with placebo (n=42) or acetylcysteine 600mg twice daily (n=41); on the day prior to and the day of administration of 75 ml of nonionic, low-osmolality contrast agent. Both groups received saline hydration adjusted for weight. The endpoint studied was changes in serum creatinine concentration. BUN levels were examined also to ensure that the change in creatinine reflected a change in renal function and not just a drug-induced change in creatinine excretion. Results: At 48 hours after the administration of contrast, the acetylcysteine treated group had a mean creatinine 0.5 mg/dl lower than the control group. The serum creatinine of the treatment group decreased from 2.5 + 1.3 mg/dl to 2.1 + 1.3 mg/dl (p<0.001) while that of the control group increased from 2.4 + 1.3 to 2.6 + 1.5 mg/dl. A simultaneous examination of BUN demonstrated a decrease from 51 + 28 mg/dl to 44 + 29 mg/dl in the treatment group (p<0.001) and an increase from 44 + 26 mg/dl to 47 + 29 mg/dl in the control group. An acute reduction in renal function was defined as an increase in creatinine greater than 0.5 mg/dl and occurred in 1/41 of the treatment group and in 9/42 of the control group (p=0.01). Comment: The results of the study showed a mean difference in the post-radiocontrast serum creatinine concentration of 0.5 mg/dl between the acetylcysteine and control group. This effect represented a benefit that was in addition to intravenous hydration, which was administered to both groups. Although this difference was statistically significant, the clinical importance of this effect remains to be proven since no patient in either group developed renal failure or required dialysis. Studying a larger group of high risk patients may be needed to demonstrate clinically important differences in outcome. Patients in the study were given a reasonably large dose of contrast, but were given only nonionic, low-osmolality contrast that has been associated with a lower risk of radiocontrast-induced nephropathy. It is possible that acetylcysteine may be less effective in response to a more toxic radiocontrast agent. It is also possible that use of a more toxic radiocontrast agent may unmask the clinical effectiveness of acetylcysteine and not just its effect on laboratory tests of renal function. Finally, only one dosing regimen for acetylcysteine was tested, but there were no adverse reactions or side effects attributed to acetylcysteine. In conclusion, a well designed and conducted study demonstrated a beneficial effect of acetylcysteine for preventing an increase in laboratory parameters of renal dysfunction in patients with pre-existing renal disease receiving radiocontrast agents. Treatment with acetylcysteine was started one day before administration of the contrast agent and was continued for a total of 48 hours. Based on these findings, when feasible, prophylactic therapy with acetylcysteine together with intravenous hydration may be indicated in selected patients with renal insufficiency who require preoperative or intraoperative angiography.
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