Pharmacotherapy

Medical Management

The priority is to rapidly reduce shear forces on the dissected aorta by controlling heart rate and lowering blood pressure. This requires careful selection of pharmacologic agents that reduce aortic wall tension without increasing shear stress by excessive reflex tachycardia or inotropy.

Goals of Medical Therapy:

• Heart rate <60 bpm
• Systolic BP 100-120 mm Hg
• Mean arterial pressure 60-80 mm Hg
• Avoid increased dP/dT or reflex tachycardia

First Line Agents:

Intravenous Beta Blockers:

• Esmolol: Short-acting beta-1 selective blocker. Loading dose 500 mcg/kg over 1 minute followed by infusion at 50-200 mcg/kg/min titrated to heart rate goal. Has very short half-life if adverse effects occur.
• Labetalol: Combined alpha/beta blocker. Bolus dosing of 20 mg IV push every 10 minutes (up to 300 mg) until heart rate goal achieved, then infusion 1-2 mg/min titrated up to 200 mg/hr.
  • The alpha antagonism causes peripheral vasodilation to complement the beta effects of lowering heart rate and contractility. Labetalol does not have active metabolites so effects dissipate quickly after stopping the infusion.

• Metoprolol: Beta-1 selective blocker. 5 mg IV every 5 minutes (up to 15 mg total) then 25-50 mg orally every 6 hours.

Beta blockers reduce shear stress by decreasing heart rate, contractility, and dP/dT. They are first line agents and the cornerstone of medical management. Continuous IV infusions allow titration to prompt heart rate control. The choice among these agents depends on the clinical scenario, need for very short-term control, and contraindications. Esmolol provides the most rapid onset and titratability but requires a continuous infusion. Labetalol has the advantage of combined alpha and beta effects. Metoprolol can be transitioned easily to oral therapy. The beta blockade should continue for at least 72 hours after surgery or until the dissection is stabilized on imaging.

Second Line/Adjunctive Agents:

• Nicardipine: Intravenous dihydropyridine calcium channel blocker. Initial infusion at 5 mg/hr, increasing by 2.5 mg/hr every 5 minutes (max 15 mg/hr) to achieve BP target. Useful if beta blocker contraindicated or additional agent needed.
• Clevidipine: Rapid-acting intravenous dihydropyridine calcium channel blocker with very short half-life. Starting dose 1-2 mg/hr, doubling every 90 seconds until BP approaches goal, then increasing by less than double to finely titrate. Useful for perioperative blood pressure management.
• Sodium nitroprusside: Direct vasodilator. 0.25-0.5 mcg/kg/min infusion, increase by 0.5 mcg/kg/min every 5 minutes, maximum 8 mcg/kg/min. Often used in combination with beta blocker for severe hypertension.
  • Requires invasive arterial monitoring during infusion.

• Hydralazine: Direct vasodilator. Intermittent IV bolus dosing of 5-20 mg every 4-6 hours as needed for BP control. May cause reflex tachycardia.

These agents provide additional options for blood pressure control in patients inadequately responsive to beta blockade. They should be used cautiously and with concurrent beta blocker to prevent reflex tachycardia and increased shear stress. Calcium channel blockers, specifically the intravenous dihydropyridine agents nicardipine and clevidipine, provide options for additional blood pressure management when beta blockers alone are insufficient. They reduce systemic vascular resistance through arteriolar dilation. Key considerations when using these agents:

• They do not treat the underlying pathophysiology or provide rate control, so should not be used as monotherapy
• Reflex tachycardia is common, requiring concurrent beta blockade

Pain Management:

• Morphine: 0.1 mg/kg IV bolus followed by 2-4 mg IV every 5-15 minutes titrated for pain relief.
• Fentanyl: 1-2 mcg/kg IV bolus followed by 1 mcg/kg IV every 30-60 minutes for pain control.

Adequate analgesia helps control pain, anxiety, and catecholamine surges that increase shear stress. It allows smoother titration of antihypertensive therapy. Careful monitoring for respiratory depression is needed.

Other Pharmacotherapy Considerations

• Avoid inotropic or chronotropic agents like dopamine, dobutamine, and epinephrine which increase shear stress.
• Manage volume status carefully, as aggressive volume resuscitation can worsen dissection.
• Attentive monitoring is required during transitions of care such as postoperative period.
• Provide in-depth patient education regarding medications, goals of therapy, adherence, and follow-up needs.

Surgical and Endovascular Management

Type A Dissections

• Require emergency surgical repair to prevent propagation, fatal complications, and rupture
• Surgery involves ascending aortic replacement with possible arch reconstruction

Indications for surgery:

• All type A dissections
• Type B dissections involving ascending aorta (DeBakey type I)
• Dissection complications: tamponade, coronary occlusion, uncontrolled pain or hypertension

Type B Dissections

• Initially managed medically unless complicated
• Endovascular repair with TEVAR may be used for malperfusion or other complications
• Uncomplicated type B dissections have 5-year survival around 75% with medical therapy alone

TEVAR may be considered if:

• Refractory pain, hypertension, or end-organ malperfusion
• Early aortic expansion >5mm diameter increase
• Large entry tear >10mm
• False lumen thrombosis <25% of total lumen

Surveillance/Follow-Up

• Serial imaging (CT or MRI) to monitor dissection healing and assess complications
• Repeat imaging at 1, 3, 6, and 12 months, then annually
• Monitor BP control and medication adherence
• Counsel on lifestyle modification and risk factor control
• Assess indications for surgical or endovascular intervention