Aortic Cross-Clamping

The pathophysiology of aortic cross-clamping and unclamping is complex and depends on many factors, including the level of cross-clamp, the extent of CAD and myocardial function, the degree of periaortic collateralization, the blood volume and distribution, the activation of the sympathetic nervous system, and the anesthetic agents and techniques. Most abdominal aortic reconstructions require clamping at the infrarenal level. However, clamping at the suprarenal and supraceliac levels is required for suprarenal aneurysms and renal or visceral reconstructions and is frequently necessary for juxtarenal and inflammatory aneurysms and aortoiliac occlusive disease with proximal extension. As endovascular repair becomes more common, an increasing proportion of patients for open repair will have anatomically complex aneurysms, many of which will require suprarenal cross-clamping. These higher levels of aortic occlusion have a significant impact on the cardiovascular system as well as on other vital organs rendered ischemic or hypoperfused. Ischemic complications may result in renal failure, hepatic ischemia and coagulopathy, bowel infarction, and paraplegia.

Hemodynamic and Metabolic Changes

The hemodynamic changes associated with aortic cross-clamping and unclamping are summarized in Table 52-9 and Table 52-10 . The systemic cardiovascular consequences of aortic cross-clamping can be dramatic, depending primarily on the level at which the cross-clamp is applied. Arterial hypertension is the most consistent component of the hemodynamic response to aortic cross-clamping at any level. Cross-clamping of the aorta at or above the diaphragm can result in profound increases in arterial blood pressure^{[215] [216]} unless diverting circulatory support or intravenous vasodilators are used.^{[215] [217]} This increase in arterial blood pressure is most likely due to the sudden increase in impedance to aortic blood flow and the resultant increase in systolic ventricular wall tension or afterload.

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Cross-clamping of the proximal descending thoracic aorta increases mean arterial, central venous, mean pulmonary arterial, and pulmonary capillary wedge pressures by 35%, 56%, 43%, and 90%, respectively, and decreases cardiac index by 29%.^[215] Heart rate and left ventricular stroke work are not significantly changed. Supraceliac aortic cross-clamping increases mean arterial pressure by 54% and pulmonary capillary wedge pressure

TABLE 52-10 -- Physiologic changes and therapeutic interventions with aortic unclamping *

Hemodynamic Changes

↓ Myocardial contractility

↓ Arterial blood pressure

↑ Pulmonary artery pressure

↓ Central venous pressure

↓ Venous return

↓ Cardiac output

Metabolic Changes

↑ Total-body oxygen consumption

↑ Lactate

↓ Mixed venous oxygen saturation

↑ Prostaglandins

↑ Activated complement

↑ Myocardial-depressant factors

↓ Temperature

Metabolic acidosis

Therapeutic Interventions

↓ Inhaled anesthetics

↓ Vasodilators

↑ Fluid administration

↑ Vasoconstrictor drugs

Reapply cross-clamp for severe hypotension

Consider mannitol

Consider sodium bicarbonate

*These changes are of greater significance with longer duration of cross-clamping and with more proximal cross-clamping.

The marked increases in pulmonary capillary wedge pressure with high aortic cross-clamping have been attributed to blood volume redistribution and increased afterload. A substantial body of evidence supports the hypothesis of blood volume redistribution during thoracic aortic cross-clamping. The splanchnic circulation, an important source of functional blood volume reserve, is central to this hypothesis. The splanchnic organs contain nearly 25% of the total blood volume, of which nearly two thirds (>800 mL) can be autotransfused from the venous vasculature into the systemic circulation within seconds.^[218] Primarily because of a lower splanchnic venous capacitance, blood volume is redistributed from vascular beds distal to the clamp to the vascular beds proximal to the clamp (see Fig. 52-11 ). Passive and active mechanisms lower splanchnic venous capacitance with thoracic aortic cross-clamping. Cross-clamping the aorta above the splanchnic system dramatically reduces

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Figure 52-11 Systemic hemodynamic response to aortic cross-clamping. Preload (asterisk) does not necessarily increase with infrarenal clamping. Depending on splanchnic vascular tone, blood volume can be shifted into the splanchnic circulation, and preload does not increase. Ao, aortic; AoX, aortic cross-clamping; R art, arterial resistance. (Adapted from Gelman S: The pathophysiology of aortic cross-clamping and unclamping. Anesthesiology 82:1026–1060, 1995.)

Several animal studies that support the blood volume redistribution hypothesis merit mention. Cross-clamping the thoracic aorta in dogs results in marked increases in mean arterial and end-diastolic left ventricular pressures (84% and 188%, respectively) and no significant change in stroke volume.^[221] In this same experimental model, simultaneous cross-clamping of the thoracic aorta and the inferior vena cava resulted in no significant change in preload or mean arterial pressure ( Fig. 52-12 ). Stroke volume was reduced by 74%. By transfusing blood during this period of simultaneous clamping, the investigators reproduced the hemodynamic effect of thoracic aortic cross-clamping alone. This study also demonstrated that thoracic aortic cross-clamping is associated with a significant and dramatic increase (155%) in blood flow above the level of the clamp, whereas no change occurred with simultaneous aortic and inferior vena cava clamping. In another animal model, the proximal aortic hypertension and increased central venous pressure occurring after thoracic aortic cross-clamping were reversed by phlebotomy.^[222] Aortic cross-clamping at the thoracic and suprarenal levels both resulted in proximal aortic hypertension, but only occlusion at the thoracic level increased central venous pressure.^[223] Thoracic aortic occlusion increased blood volume in organs and tissues proximal to the clamp, whereas no such increase occurred with suprarenal aortic cross-clamping. These experimental data strongly support the hypothesis of blood volume redistribution during aortic cross-clamping and help to explain the marked differences in hemodynamic responses observed after aortic cross-clamping at different levels.^[216]

Afterload-dependent increases in preload also occur with aortic cross-clamping, usually in the setting of impaired myocardial contractility and reduced coronary reserve. The impaired left ventricle may respond to increased afterload with an increase in end-systolic volume and a concomitant reduction in stroke volume (afterload mismatch). The reduction in stroke volume may result from limited preload reserve, myocardial ischemia, or inability of the heart to generate a pressure-induced increase in

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Figure 52-12 Schematic drawing of the circulation. Compliant regions (stippled lines) of the upper and lower parts of the body and end-diastolic volumes of the left ventricle in a control state (left panel) are shown after occlusion of aorta alone (middle panel) and combined occlusion of the aorta and inferior vena cava (right panel). IVC, inferior vena cava; LV, left ventricle; PVS and PVI, pressure in compliant regions of the upper and lower body respectively; Shunt, physiologic shunt; SVC, superior vena cava. (From Stokland O, Miller MM, Ilebekk A, Kiil F: Mechanism of hemodynamic responses to occlusion of the descending thoracic aorta. Am J Physiol 238:H423–H429, 1980.)

Most clinical studies indicate that cardiac output decreases with thoracic aortic cross-clamping, whereas most animal studies show no significant change. The normal heart can withstand large increases in afterload without significant ventricular distention or dysfunction. Although impaired myocardial contractility and reduced coronary reserve are rare in animal experiments, such disorders are frequent in the elderly population undergoing aortic reconstruction. The increase in proximal aortic pressure seen with thoracic and supraceliac cross-clamping^{[215] [216]} may increase left ventricular wall stress (afterload), with resultant acute deterioration in left ventricular function and myocardial ischemia. Impaired subendocardial perfusion caused by high intramyocardial pressure may be the cause of wall motion abnormalities and changes in ejection fraction. Reflex mechanisms causing immediate feedback inhibition may also explain the reduction in cardiac output with aortic cross-clamping. For example, baroreceptor activation resulting from increased aortic pressure should depress heart rate, contractility, and vascular tone.

The metabolic effects of cross-clamping and unclamping were summarized in Table 52-9 and Table 52-10 . Cross-clamping of the thoracic aorta decreases total body oxygen consumption by approximately 50%.^{[224] [225]} For reasons that are unclear, oxygen consumption decreases in the tissues above the clamp.^[224] In clinical studies, increased mixed venous oxygen saturation occurs with aortic cross-clamping above the celiac axis.^{[226] [227]} This increase in mixed venous oxygen saturation may be explained by a reduction in oxygen consumption that exceeds the reduction in cardiac output, decreasing total body oxygen extraction.^[227] Central hypervolemia ^[221] or increased arteriovenous shunting^[228] in the tissues proximal to the aortic clamp may play a role in reducing total body oxygen extraction.

Arterial blood pressure, blood flow, and oxygen consumption distal to a thoracic aortic cross-clamp decrease by 78% to 88%,^{[220] [229] [230]} 79% to 88%,^{[221] [224]} and 62%,^[224] respectively, from baseline values before clamping. Blood flow through tissues and organs below the level of aortic occlusion is dependent on the perfusion pressure and is independent of cardiac output. ^[229] Administration of sodium nitroprusside to maintain proximal aortic pressure above the cross-clamp at preclamp levels has been shown to further reduce arterial pressure distal to the clamp by 53%.^[229] As is discussed later, these data have significant implications regarding vital organ protection during aortic cross-clamping.

The cardiovascular response to infrarenal aortic cross-clamping is less significant than with high aortic cross-clamping (see Table 52-11 ). Although several clinical reports have noted no significant hemodynamic response to infrarenal cross-clamping,^{[231] [232]} the hemodynamic response generally consists of increases in arterial pressure (7% to 10%) and systemic vascular resistance (20% to 32%) with no significant change in heart rate.^{[233] [234] [235]} Cardiac output is most consistently decreased by 9% to 33%.^{[232] [233] [235] [236]} Reported changes in ventricular filling pressures have been inconsistent.^{[216] [231] [232] [233] [234] [235] [236] [237]} Blood volume redistribution may affect preload with infrarenal aortic cross-clamping (see Fig. 52-11 ). In this situation, blood volume below the clamp shifts to the compliant venous segments of the splanchnic circulation above the clamp, dampening the expected increase in preload. Preload changes with infrarenal aortic

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Renal Function and Protection

Acute renal failure occurs in approximately 3% of patients undergoing elective infrarenal aortic reconstruction, and mortality resulting from postoperative acute renal failure is greater than 40%.^[242] Despite significant improvements in the perioperative care of patients undergoing aortic reconstruction, the high morbidity and mortality resulting from acute renal failure is largely unchanged over the past 2 decades. Much of the morbidity associated with significant postoperative renal dysfunction is nonrenal in nature. Preservation of renal function is of significant importance during aortic reconstructive surgery. Adequacy of renal perfusion cannot be assumed by urine output, because intraoperative urine output does not predict postoperative renal function. ^{[243] [244]} Procedures requiring aortic cross-clamping above the renal arteries dramatically reduce renal blood flow. Experimental studies report an 83% to 90% reduction in renal blood flow during thoracic aortic cross-clamping.^{[229] [245]} Infrarenal aortic cross-clamping in humans is associated with a 75% increase in renal vascular resistance, a 38% decrease in renal blood flow, and a redistribution of intrarenal blood flow toward the renal cortex.^[232] These rather profound alterations in renal hemodynamics occurred despite no significant change in systemic hemodynamics, and they persisted after unclamping. The sustained deterioration in renal perfusion and function during and after infrarenal aortic cross-clamping has been attributed to renal vasoconstriction, but the pathophysiology remains unknown.^{[120] [232]} Renal sympathetic blockade with epidural anesthesia to a T6 level does not prevent or modify the severe impairment of renal perfusion and function that occurs during and after infrarenal aortic cross-clamping.^[120] Although plasma renin activity is increased during aortic cross-clamping,^[246] pretreatment with converting enzyme inhibitors before infrarenal aortic cross-clamping does not attenuate the decreased renal blood flow and glomerular filtration rate. Other mediators, such as plasma endothelin, myoglobin, and prostaglandins, may contribute to the decreased renal perfusion and function after aortic cross-clamping.

Acute tubular necrosis accounts for nearly all renal dysfunction and failure after aortic reconstruction. The degree of preoperative renal insufficiency remains the strongest predictor of postoperative renal dysfunction. In addition to aortic cross-clamping-induced reductions in renal blood flow, intravascular volume depletion, embolization of atherosclerotic debris to the kidneys, and surgical trauma to the renal arteries all contribute to renal dysfunction. Mannitol, loop diuretics, and dopamine are used clinically in an attempt to preserve renal function during aortic surgery. Significant controversy exists regarding the use of these agents as well as the mechanisms by which they may offer a protective effect. Despite studies demonstrating little or no benefit,^{[247] [248] [249] [250]} it is widely believed that renal protection before aortic cross-clamping is beneficial and therefore many clinicians administer these drugs. The use of mannitol to induce an osmotic diuresis before aortic cross-clamping is ubiquitous in clinical practice. I routinely administer mannitol (12.5g/70 kg) to all patients before aortic cross-clamping. Mannitol improves renal cortical blood flow during infrarenal aortic cross-clamping. ^[251] Mannitol can reduce ischemia-induced renal vascular endothelial cell edema and vascular congestion.^[252] Other mechanisms by which mannitol may be beneficial include acting as a scavenger of free radicals, decreasing renin secretion, and increasing renal prostaglandin synthesis.^[253] Loop diuretics and low-dose dopamine (1 to 3 μg/kg/min) have been advocated to protect the kidneys from aortic cross-clamp induced injury by increasing renal blood flow and urine output intraoperatively. Some clinicians advocate the routine use of these agents for patients with preoperative renal insufficiency and for procedures requiring suprarenal aortic cross-clamping. Intraoperative use of these agents requires increased surveillance of intravascular volume and electrolytes during the postoperative period. Therapy with these agents could be harmful because of hypovolemia and resultant renal hypoperfusion. Dopamine's positive inotropic and chronotropic activity may cause tachycardia and may increase myocardial oxygen consumption in patients with limited coronary reserve. Although the prophylactic use of dopamine has been virtually abandoned, I often administer diuretic to patients with low urine output after aortic unclamping, particularly those on chronic diuretic therapy. Fenoldopam mesylate, a selective dopamine type 1 agonist that preferentially dilates renal and splanchnic vascular beds, has shown some early promise as a renal-protective agent.^{[254] [255]} However, prospective data are very limited, and further study will be required to determine if this novel agent has a role in the prevention of renal dysfunction after aortic surgery.

Most clinical studies suggest that optimization of systemic hemodynamics, including maintenance of intravascular volume, is the most effective means of renal protection during and after aortic cross-clamping.^{[256] [257] [258] [259]} I believe this is clearly the best prophylaxis against post-operative renal dysfunction. The goal is to achieve a preload adequate to allow the left ventricle to cope with cross-clamping induced changes in contractility or afterload and maintain cardiac output. However, in providing such therapy, it is equally important to avoid over-hydration, which may lead to inappropriate increases in preload or pulmonary edema in patients with decreased myocardial reserve.

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Therapeutic Strategies

Patients with preexisting impaired ventricular function and reduced coronary reserve are most vulnerable to the stresses imposed on the cardiovascular system by aortic cross-clamping. Rational therapeutic strategies to prevent the deleterious effect of aortic cross-clamping primarily include measures to reduce afterload and normalize preload. Coronary vasodilators, positive and negative inotropes, and controlled volume depletion (i.e., phlebotomy) may be used selectively.

Patients with impaired ventricular function requiring supraceliac aortic cross-clamping are the most challenging. Myocardial ischemia, reflecting an unfavorable balance between myocardial oxygen supply and demand, may result from the hemodynamic consequences of aortic cross-clamping. Controlled (i.e., slow clamp application) supraceliac aortic cross-clamping is important to avoid abrupt and extreme stresses on the heart. Afterload reduction, most commonly accomplished by use of sodium nitroprusside (predominantly an arteriolar dilator), is necessary to "unload" the heart and reduce ventricular wall tension. In a large series of patients requiring cross-clamping of the descending thoracic aorta, stable left ventricular function was maintained during cross-clamping with sodium nitroprusside.^[217] The researchers also concluded that sodium nitroprusside allowed adequate volume loading before unclamping, which resulted in stable unclamping hemodynamics. Normalization of preload involves careful fluid titration and vasodilator administration. Infusion of nitroglycerin during abdominal aortic surgery has been shown to maintain ventricular function during the cross-clamp period.^[260] During thoracic aortic cross-clamping, isoflurane can provide hemodynamics comparable to those provided by sodium nitroprusside.^[225] Amrinone provides hemodynamic control equivalent to that of sodium nitroprusside during abdominal aortic surgery.^[261] Blood flow below the clamp, which is pressure dependent,^[229] decreases during therapy with vasodilators.^{[224] [229]} Vital organs and tissues distal to the clamp are exposed to reduced perfusion pressure and blood flow. In patients without evidence of left ventricular decompensation or myocardial ischemia during supraceliac aortic cross-clamping, a proximal aortic mean arterial pressure of up to 120 mm Hg is acceptable. Although infrequent, maintenance of adequate cardiac output may require active intervention with inotropic agents. In general, anesthetic agents that depress myocardial function are avoided during aortic procedures.