Abstract
Peripheral arterial disease (PAD) is characterized by atherosclerotic occlusive disease of the lower extremities. PAD, cerebrovascular disease, and coronary artery disease are the three major syndromes of atherosclerosis. PAD affects at least 8 to 12 million Americans and is associated with significant morbidity and mortality and decreased quality of life. We will discuss risk factors, clinical features, anesthetic considerations, and treatment strategies for patients with peripheral vascular disease
Keywords
arterial, ischemia, peripheral vascular disease, revascularization
Case Synopsis
A 74-year-old woman with a long-standing history of insulin-dependent diabetes, hypertension, chronic kidney disease, and a 50 pack-year smoking history requires right lower limb surgical revascularization due to lifestyle-limiting claudication. The patient is on carvedilol, simvastatin, lisinopril, and insulin. She describes chronic angina after ascending over two flights of stairs that resolves with rest. A dobutamine stress echocardiogram demonstrates a single segment of basal inferior hypokinesis at rest and on stress imaging. General anesthesia with endotracheal intubation is planned. There is a possibility of using upper extremity vessels as graft material. An hour after uneventful surgery, while the patient is in the recovery unit, the surgeon recognizes impending graft thrombosis after the loss of Doppler signals. The graft must be reexplored in the operating room.
Problem Analysis
Definition
Peripheral arterial disease (PAD) is characterized by atherosclerotic occlusive disease of the lower extremities. PAD, cerebrovascular disease, and coronary artery disease are the three major syndromes of atherosclerosis. PAD affects at least 8 to 12 million Americans and is associated with significant morbidity and mortality and decreased quality of life.
The strongest risk factors for PAD are diabetes and smoking. Other well-known risk factors are advanced age (>60 years), hypertension, and hyperlipidemia. The Fontaine and Rutherford classification systems are used to grade the severity of clinical symptoms reported by patients, with a higher grade indicating a higher severity of disease. The Rutherford scoring system is more commonly used in newer scientific literature. These two classification systems are based on an ischemia model to assess the risk of amputation versus the benefit of revascularization and hence may not provide the same prognostication in diabetic patients with threatened limbs.
When PAD is symptomatic, the most common complaint is intermittent claudication (IC). However, most patients are either asymptomatic or have symptoms other than IC.
On the other end of the spectrum are patients who present with life-threatening or acute limb ischemia (ALI), manifested by pain at rest; gangrene; and chronic, nonhealing wounds. In reality, ALI is a complex interplay of multiple pathogenetic mechanisms rather than progressive atherosclerosis. Acute limb ischemia (ALI) is defined as a sudden (<2 weeks) decrease in limb perfusion that threatens the viability of the limb. The degree of ischemia is related to the extent of occlusion, distal runoff, and maturity of collateral arteries. Limb viability is acutely threatened in ALI as opposed to chronic limb ischemia (CLI) because there is insufficient time for collateral blood supply to circumvent the occlusion.
The incidence of ALI requiring hospitalization in the United States is approximately 26 per 100,000 compared with approximately 200 per 100,000 per year for CLI. Patients who present with acute limb ischemia are systemically ill and have three times higher risk of perioperative mortality (approximately 10% to 25%) compared with patients with CLI. Hence, accurate and prompt diagnosis is essential to increase the chances of limb preservation and to decrease mortality. These patients require emergent revascularization within 6 hours to prevent complete limb ischemia and extensive tissue necrosis.
Clinical features of acute limb ischemia are commonly grouped into a mnemonic known as the six P s: paresthesia (or anesthesia), pain, pulselessness, pallor, poikilothermia (limb’s temperature equalizes with ambient temperature), and paralysis. Apart from paralysis and anesthesia, these clinical signs and symptoms are often nonspecific and have poor correlation with completeness of vascular occlusion. Pain on squeezing the affected muscle indicates infarction and impending irreversible tissue damage. If the patient still has the ability to wiggle his or her fingers or toes and sensations are still present, the limb is likely salvageable with urgent revascularization within 6 hours. Attempting revascularization 10 to 12 hours after severe ischemia is often unsuccessful due to sequelae of the systemic inflammatory response and ischemia-reperfusion injury.
Causes of acute limb ischemia can be broadly categorized into (1) acute emboli (60% of cases), from the heart (80%) or a diseased artery (20%), and (2) acute thrombosis (30% of cases) of a limb artery (e.g., popliteal aneurysm) or bypass graft. Other causes include trauma (blunt or penetrating), malperfusion (due to aortic or isolated peripheral artery dissection), iatrogenic injury (postprocedural, intraarterial drug injection), coagulopathy (e.g., heparin-induced thrombocytopenia [HIT] syndrome), and sepsis (particularly pneumococcal and meningococcal). Of note, venous gangrene may be mistaken for acute limb ischemia.
At presentation, 25% of patients with ALI will be treated medically, 50% to 60% will undergo revascularization, and 25% will undergo primary amputation. The major treatment goals for ALI include limb salvage, wound healing, pain control, reduction in overall cardiac risk, and improvement in quality of life. Because such patients are at risk for imminent limb loss, surgery is semiurgent or urgent. During revascularization, aortoiliac (inflow) or distal (outflow) obstructions are bypassed with axillofemoral or femoropopliteal distal bypass grafts, respectively. Also, successful surgery and long-term survival of the graft depend on blood flow through the graft, blood coagulability, and the future development of atherosclerotic changes in the graft. Anesthesia care can have an important impact on immediate and longer-term outcomes.
Recognition
Peripheral vascular surgery, particularly suprainguinal operations, are classified as high-risk procedures. Therefore careful attention to metabolic and cardiac status is critical. This, combined with the high prevalence of clinical risk factors, translates into increased risk for perioperative cardiac complications. These risk factors (Revised Cardiac Risk Index [RCRI]) include a history of ischemic heart disease, congestive heart failure, cerebrovascular disease, diabetes with preoperative treatment with insulin, and serum creatinine greater than 2 mg/dL. A patient with three or more risk factors has a 5.4% risk of major cardiac complication. Perioperative myocardial infarction (MI) has a complex pathophysiology, but the major contributing factors arise from coronary plaque rupture (type I MI, T1MI) and the mismatch of myocardial oxygen supply demand (type II MI, T2MI). All patients who present with active cardiac conditions, including unstable coronary syndromes, decompensated heart failure, significant arrhythmias, and severe valvulopathies, should undergo evaluation and treatment before surgery.
Risk Assessment
Perioperative MI is the most common cause of death after major vascular surgery. Several studies suggest that perioperative MI is often asymptomatic and commonly occurs within the first 48 hours after surgery, with strong association for transitioning into a symptomatic MI and increased 30-day mortality. Angiotensin-converting enzyme (ACE) inhibitors may have a protective role in the modification of renin-angiotensin system (RAS)–induced atherosclerosis. Drugs that target the RAS, such as ACE inhibitors and angiotensin-II receptor blockers (ARBs), are widely used to lower blood pressure. Newer research based on animal models suggests they may also have an additional role in decreasing atherosclerosis that is independent of their blood-lowering effect. The Heart Outcomes Prevention Evaluation (HOPE) trial of 9297 patients over 55 years of age established that high plasma renin activity was a major predictor of vascular events and mortality, which suggests that these patients could benefit from the inhibition of the RAS.
Patients with PAD are often on cardiovascular medications that have been recommended to decrease cardiovascular risk, including antiplatelet drugs, β-blockers and statins. High-risk patients (i.e., those with an RCRI index score ≥3 on aspirin, β-blocker, and statin therapy) had a threefold reduction in risk of perioperative MI and mortality at 30 days and 1 year. Additionally, there was no demonstrable increase in moderate or severe bleeding due to aspirin use in these patients. The survival benefit of antiplatelet and statin therapy preoperatively and at discharge was present at 5 years after vascular surgery. In a large prospective study that queried the association between bleeding complications from peripheral vascular surgery and antiplatelet use (aspirin and/or clopidogrel), the authors demonstrated the risk of reoperation for bleeding to be not significantly different across antiplatelet regimens.
According to the 2014 American Heart Association (AHA)/American College of Cardiology (ACC)/Centers for Disease Control and Prevention (CDC) guidelines, a blood pressure goal of 139/89 mm Hg or less was recommended regardless of age. Other guidelines, such as the JNC-8, suggest a higher cutoff of less than 150/90 mm Hg for patients over age 60 years. This less stringent recommendation may change depending on the results from the SPRINT trial of 2015—a randomized controlled trial with more than 9000 patients over age 50 years that was ended early due to evidence that a more aggressive blood pressure target of 120/80 mm Hg had a significant impact on reducing cardiovascular and cerebrovascular morbidity and mortality. Generally speaking, patients with stage I hypertension (systolic blood pressure [SBP] 140 to 159 mm Hg or diastolic blood pressure [DBP] 90 to 99 mm Hg) or stage II hypertension (SBP ≥160 mm Hg or DBP ≥100 mm Hg) should be treated with lifestyle modification, and if not adequately controlled at 6 months, a thiazide diuretic alone or in combination with an ACE inhibitor, ARB, or calcium channel blocker should be initiated.
Smoking cessation should be encouraged due to its deleterious effects on vascular inflammation, accelerated atherosclerosis, and ultimately bypass graft failure. Long-term outcomes associated with active smoking include increased risk of limb loss, MI, and death. With respect to pulmonary complications, smoking cessation initiated less than 4 to 8 weeks before surgery does not carry additional risk compared with patients who continue smoking until surgery. To better predict pulmonary complications in patients who smoke, pulmonary function tests may be appropriate.
Monitoring
Indicated monitoring includes at least a two-lead electrocardiogram with precise placement of V 4 or V 5 leads, surface pulse oximetry, end-tidal carbon dioxide and inhalational anesthetic monitoring, and noninvasive blood pressure monitoring. Invasive monitoring is indicated for some patients, especially those with symptomatic or severe cardiovascular disease (e.g., stage III or IV heart failure, symptomatic arrhythmias). Such monitoring includes an arterial line, central venous pressure, transesophageal echocardiography, and possibly a pulmonary artery catheter. These are placed before or after anesthesia induction. With severe hypertension, poor left ventricular function (ejection fraction ≤0.35), or symptomatic coronary artery disease, preinduction invasive monitoring allows tighter control of hemodynamic changes during induction and tracheal intubation and during periods of increased cardiovascular stress. The anesthetic technique (regional anesthesia [RA] vs. general anesthesia [GA]) should not affect the decision to institute central venous pressure or pulmonary artery catheter monitoring. Central lines may be required for patients with poor peripheral access or when arm veins will be used as conduits for surgery. Transesophageal echocardiography is useful for monitoring cardiac function and volume status when GA is used, especially for hemodynamically unstable patients or if a cardiac (atrial fibrillation) or aortic (unstable plaque) source for thromboembolism is present.
Management
Regarding anesthetic technique, primary concerns focus on the surgical revascularization procedure, the patient’s tolerance of the anesthetic and surgery (which often takes many hours), and preoperative cardiopulmonary risk factors. Another important concern is the effect of anesthetic technique—RA versus GA—on the success of revascularization and perioperative outcomes. The following factors should be considered.
Sympathectomy
This procedure dilates the venous capacitance bed to reduce cardiac preload, thus increasing fluid requirements to maintain cardiac output. It also reduces systemic vascular resistance. If this decreases cardiac afterload and work, it may improve global and regional left ventricular function for the duration of the sympathetic block. For example, a cardiac sympathectomy induced by a thoracic epidural would increase myocardial oxygen supply and decrease cardiac work by lowering wall tension, heart rate, and afterload. Furthermore, these patients exhibit lower levels of electrocardiographic evidence of myocardial ischemia compared with controls.
Sympathetic block may also reduce stress-related hypercoagulability and the frequency of venous thromboembolism. Tuman and colleagues reported a 2.5% versus 20% graft failure rate randomly comparing RA and GA, respectively, suggesting that neuraxial anesthesia during limb revascularization has beneficial effects on maintaining graft patency and viability in the early postoperative period.
Stress Response
The stress response activated during surgery may be attenuated by RA. Spinal anesthesia may produce a greater reduction in the neuroendocrine stress response than epidural anesthesia as evidenced by lower levels of intraoperative cortisol, noradrenaline, and total catecholamine levels in the former group. Furthermore, there are profound changes to the metabolic, immune, and neurohormonal systems that RAs may favorably influence—mismatches in myocardial oxygen supply-demand, arterial vasoconstriction, hypercoagulability and fibrinolysis, reduced urinary output, hyperglycemia, sodium and water retention, wound infections, cancer recurrence, and postoperative delirium and cognitive dysfunction. Additionally, epidural analgesia with a combination of local anesthetic and opioid initiated before incision will abolish stress response to surgery on the lower limbs greater than systemic opioids alone.
Regional Versus General Anesthesia
Although it is difficult to compare studies of anesthetic techniques, medications, and surgical factors related to peripheral vascular disease (PVD), recent prospective randomized trials have found no difference in mortality rates between spinal or epidural RA and GA ( Table 69.1 ). The lack of reported differences in outcome may be attributed to improved cardiovascular management in these trials compared with earlier ones.