Hello everyone!
I’d like to start off by saying it’s an honor to contribute to this amazing group! I am one of three pharmacy residents at SUNY Downstate Medical Center and have had the opportunity of working with some of you at UHB. Starting this month, I will be posting about various topics pertinent to medications in the ED or critical care setting. Please feel free to let me know if there are certain issues you would be interested in reading about, and I will definitely address them in future postings.
Here is this month’s topic…
Hypertensive emergency management in the setting of aortic dissections:
Hypertension is a disease that affects almost 30% of our nation’s population. Along with this statistic is the rising incidence of hypertensive crises. Associated with acutely elevated blood pressures (BP), it is essential to promptly address and control a patient’s blood pressures as well as assess for end-organ damage. Common end-organ complications of hypertensive emergencies are intracrnial aneurysms, stroke, subarachnoid hemorrhage, myocardial infarction, and aortic dissections. The 2003 JNC7 Guidelines recommends using parenteral agents to rapidly bring down the MAP by 20-25% within the first 60 minutes, then further reduce to 160/100 over the next 2-6 hours if stable and eventually reaching baseline over 24-48 hours. (Exception: patients with acute ischemic stroke should have cautious lowering of MAP by 10-15% to allow for adequate cerebral perfusion.)
Selection of antihypertensive agents should consider target organ at risk as well as pharmacologic parameters. A review article by Rhoney and Peacock summarizes ideal agents for specific indications:
Rhoney and Peacock. AJHP 2009; 66: 1343-52.
*Nesiritide and phentolamine are not used much in the clinical setting anymore and/or are not available for use.
Aortic dissections are truly medical emergencies in which there is a separation of the layers within the aortic wall. It is diagnosed in approximately 1/10,000 patients and occurs more commonly in black males ages 50-65. Aortic dissections are associated with a very high mortality rate with some estimates up to 75%. It is imperative to reduce blood pressure as rapidly as possible. In fact, BP should be aggressively lowered more than the generally recommended 20-25% MAP reduction to a systolic BP < 120 mmHg and heart rate < 60 bpm. By rapidly decreasing systolic BP, there is also a decrease in the shearing force against the aortic wall and myocardium, thus preventing propagation of the intimal tear.
After the initial management of blood pressure and pain control, the next step is surgery. Unfortunately, not all patients with aortic dissections are candidates for surgery. Some exclusion factors are: age > 70 years, low BP or shock at presentation, renal failure, MI, and stroke. Yet, even without surgery, there is data that supports survival with just medical management. Feldman, et al. showed that there is greater percentage of survival in surgical patients in the initial 3 months. However after that time frame, long-term survival (studied up to 10 years) was not significantly different from those medically managed.
So what constitutes medical management?
The pathophysiology of aortic dissections is driven by hypertension and shearing forces that add stress to the aortic wall. Therefore, the goal of drug therapy is to provide anti-impulse therapy, which is defined as reducing BP and – more importantly – decreasing the rate of change of shearing force (dP/dt). Dissection progression is not dependent on high pressure or high flow; rather it depends on the strength of pulsation via left ventricle contraction. Thus, medications that provide negative inotropy (↓ dP) and negative chronotropy (↓ dt), e.g. β-blockers, would achieve this goal and reduce the shearing force against the aortic wall.
Sanz, et al. showed that dissection progression corresponds with increased dP/dt. Furthermore, they were able to demonstrate changes in the slope for specific medications. Nitroprusside is a potent vasodilator that reduces both preload and afterload. The figure below shows rapid lowering of BP, however the slope is actually increased secondary to reflex tachycardia (↓dP/↓↓dt). On the other hand, β-blockers have a moderate decrease in BP from baseline, but provide chronotropic reduction leading to a decreased slope (↓dP/↑dt). Though not demonstrated, a combination of both nitroprusside and β-blocker would presumably decrease the peak BP (↓ dP), lengthen time (↑ dt), and therefore decrease the slope (↓↓dP/↑dt), i.e. strength of pulsation.
Nitroprusside vs. Nitroglycerin vs. Nicardipine
A couple more points before concluding: some of you may ask why nitroprusside versus nitroglycerin? Do all β-blockers have the same effect? Despite its association with thiocyanate/cyanide toxicity, nitroprusside has the advantage of dilating both venous and arteriolar systems via donation of exogenous nitric oxide (NO), whereas nitroglycerin provides mostly venous vasodilation via circulation of endogenous NO which eventually leads to nitrate tolerance. For this reason, nitroprusside is a faster and more effective BP lowering agent than nitroglycerin. Caution should definitely be taken in patients with renal insufficiency when starting nitroprusside infusion. However thiocyanate/cyanide toxicity occurs infrequently and is usually associated with prolonged infusions (>3 days) at high doses (>3mcg/kg/min).
Finally, nicardipine is dihydropyridine calcium channel blocker that is commonly used for rapid BP reduction. Especially beneficial in patients with aortic aneurysms or intracerebral hemorrhage, nicardipine penetrates the blood-brain barrier and prevents vasospasms. Despite its excellent BP-lowering effects, nicardipine can cause reflex tachycardia and increase the slope of the aortic pressure curve (↓dP/↓↓dt).
Which beta blocker is best?
When choosing a β-blocker, one must consider which receptors are inhibited. β1? β2? Both? Others? First-generation β-blockers (propranolol, nadolol, timolol, sotalol, pindolol) are non-selective agents and bind to β1- and β2-receptors. Consequently, they affect cardiac as well as peripheral vasculature. Second-generation β-blockers (metoprolol, esmolol, bisoprolol, atenolol, acebutalol) selectively bind to β1-receptors in cardiac tissue, therefore lowering heart rate and cardiac output. Mixed receptor β-blockers (labetalol, carvedilol) also antagonize α1-receptors which provide additional vasodilation and BP reduction. Of these agents, IV formulation is available for esmolol, labetalol, metoprolol, atenolol. Esmolol and labetalol can be run as continuous infusions. A disadvantage of labetalol is the concentration of the bag; 100mg/100mL infused at a rate of 1-3 mg/min provides a volume of 60-180 mL/hour. Obviously providing such a large amount of fluids can negate the efforts to reduce BP and requires frequent changing of IV bags by nurses. A solution to this is to instead use the more concentrated formulation of 300mg/100mL.
In Summary:
- Choose an IV agent best suited for the specific hypertensive emergency you are treating – base your choice on target end organ and pharmacologic parameters.
- For aortic dissections, it is imperative to control blood pressure, inotropy, and chronotropy to quickly decrease BP and strength of pulsation (↓↓dP/↑dt).
- Using potent vasodilators (e.g. nitroprusside) and β-blockers (e.g. esmolol, labetalol) will achieve this effect. Labetalol should be ordered as the most concentrated formulation of 300mg/100mL to avoid volume overloading and to ease nursing administration.
- Other agents such as nicardipine can be considered for hypertension and inotropic reduction; however, it does not decrease HR.
Reviewed by: Dr. Alan Hui, Dr. Teresa Chan
References:
JNC7. JAMA 2003; 290(2): 197.
Rhoney and Peacock. AJHP 2009; 66: 1343-52.
Wiesenfarth JM. Acute aortic dissection. Medscape. Aug 2015.
Feldman, et al. Ann Thorac Cardiovasc Surg 2009; 15(5): 286-93.
Sanz J, Einstein AJ, Fuster V. Acute aortic dissection: anti-impulse therapy. In: Elefteriades J ed.; Acute Aortic Disease. New York: Informa Healthcare, 2007; pp 229–50.
Sarah
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