Reduction Of Dpdt And Treatment Of Hypertension

The primary objectives of pharmacological therapy are the reduction of the rate of rise of systolic aortic pressure due to left ventricular ejection of blood (dp/dt) and the lowering of the systolic blood pressure. Such medical therapy is accepted as the initial treatment for virtually all patients in whom aortic dissection is suspected, even before a definitive diagnosis is made, and should be continued thereafter once the diagnosis is confirmed. All patients with acute aortic dissection should be managed in an acute care setting for intensive medical therapy, hemodynamic monitoring, and cardiac telemetry. When dissection is suspected, patients should be monitored with an automatic blood pressure cuff if hemodynamically stable. However, if patients are unstable or after dissection is confirmed, a radial arterial line should be placed for continuous accurate blood pressure monitoring. It is essential at the outset to measure blood pressures in both arms, as there is a blood pressure differential in 15% of cases. Should a blood pressure differential exist, one must make certain to monitor and treat the higher of the two pressures, as this more accurately reflects the actual aortic pressure. Therefore, the arterial line should be placed on whichever side has the higher pressure.

The therapeutic goal is a reduction of systolic blood pressure to 100 to 110 mmHg and the heart rate to 50-60 beats per minute or the lowest level commensurate with adequate vital organ (cardiac, cerebral, renal) perfusion. In otherwise healthy patients, a systolic blood pressure of 100 mmHg is well tolerated and thus a reasonable goal, but in older patients with atherosclerotic vascular disease it may be necessary to maintain a systolic blood pressure in the range of 120-130 mmHg, or greater. One should monitor mental status, cardiac symptoms, and urine output on a frequent basis to see that the organ perfusion is adequate. Also, all caregivers should be familiar with the hemodynamic targets and notify the physician if those targets cannot be maintained.

Beta-blocking agents are the mainstay of pharmacologic therapy given their ability to reduce dp/dt. In the acute setting, intravenous agents are preferred, given their rapid onset and one's ability to titrate doses to achieve the desired effect. Therapy should be administered initially in incremental doses until satisfactory beta blockade is achieved, usually indicated by a reduction in heart rate to 50-70 beats/min. However, sometimes the starting blood pressure is too low to allow sufficient doses of beta blockers to achieve this target heart rate.

Intravenous propranolol is widely used in treating acute aortic dissection because it is relatively short acting and can be administered in either bolus fashion or as a continuous infusion. One should begin with a propranolol dose of 1 mg intravenously every 3-5 min until the desired effect is achieved, and then additional doses should be given intravenously every 3-6 hours or administered as a continuous intravenously infusion. Another commonly used beta blocker in this setting is labetalol, which acts as both an alpha- and beta-adrenergic receptor blocker. It is especially useful among patients with aortic dissection who have marked hypertension on presentation, as it will serve to significantly lower arterial pressure as well as to reduce dp/dt. The initial dose of labetalol is 20 mg intravenously, followed by repeated doses of 40-80 mg every 10-15 min until the heart rate and blood pressure have been controlled or a maximum total dose of 300 mg has been reached. Patients should then be started on a continuous intravenous infusion starting at 2 mg/min and titrating up to 5-10 mg/min.

Esmolol is an ultra-short-acting beta blocker, and because the infusion can be abruptly discontinued if necessary, it is especially useful in patients starting with relatively normal blood pressures in whom one still wants to achieve a reduction in dp/dt. Esmolol may also be preferable when there is uncertainly about the safety and tolerance of beta blockers, such as in patients with a history of obstructive pulmonary disease who may be at risk for bronchospasm. However, esmolol is not a very potent beta blocker, so once the safety of therapy has been established, it may be preferable to switch over to a more effective but cardioselective beta blocker, such as intravenous metoprolol. Esmolol is administered as a 0.5 mg/kg intravenous bolus followed by continuous infusion at 50 ^g/kg/min and titrated up to 200 ^g/kg/min.

Beta blockers are the first line of medical therapy but are often insufficient to adequately control the hypertension that may accompany acute aortic dissection. The preferred second line agent to add in this setting is the intravenous vasodilator sodium nitroprusside. It is infused at an initial rate of 20 ^g/min, which is then titrated progressively upward to a dose as high as 800 ^g/min, as required to achieve and maintain the desired blood pressure response. Although nitroprusside is extremely effective, it should also be recognized that when used alone in can actually cause an increase in dp/dt, which could be detrimental in the setting of acute aortic dissection. Therefore, it is essential that one initiate therapy with a beta blocker prior to administering nitroprus-side. For those patients with acute or chronic renal insufficiency, the intravenous vasodilator fenoldopam may be preferable to sodium nitroprusside2.

When contraindications exist to the use of beta blockers (e.g., sinus bradycardia, atrioventricular block, congestive heart failure, or bronchospasm), one should consider the use of other agents to reduce arterial pressure and dp/dt. Calcium channel antagonists may be used safely among those with bronchospasm. Diltiazem and verapamil have vasodilator and negative inotropic effects, and both can be administered intravenously, so they are well suited for the treatment of aortic dissection. Nifedipine has little effect on heart rate or conduction, so it may be ideal for the patient who has bradycardia or heart block. Nifedipine also has the advantage that it can be administered via the sublingual route, permitting rapid initiation of therapy while intravenous access is established and other medications are being prepared. Conversely, an important limitation of nifedipine is that it has little effect in reducing dp/dt.

On occasion, acute hypertension may result when a dissection flap compromises one of the renal arteries, thereby causing the release of large amounts of renin. In this situation, the most efficacious antihypertensive may be the intravenous angiotensin-converting enzyme (ACE) inhibitor enalaprilat, which is administered initially in doses of 0.625 mg every 4-6 hours and the dose then titrated upward.

Finally, the majority of patients with acute aortic dissection have significant pain, and the pain itself may exacerbate hypertension and tachycardia. Often reducing arterial pressure will relieve the presenting pain, likely due to a decrease in the tension on the dissected aortic tissue. However, when pain persists it should be treated promptly with intravenous morphine sulfate. In some instances a patient's fear and anxiety may predominate in the acute setting, in which case intravenous anxiolytics may be helpful.

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