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to 90. His mentation improved, he said he was having no chest discomfort, his lungs were clear to auscultation, and the S3 was no longer audible. The following day his previous oral anti- hypertensive regimen was reinstituted. 2 days later, he had an exercise stress SPECT myocardial perfusion study, which demon- strated no evidence of ischemia, and an ejection fraction of 60 %. He was discharged home the following day.
Principles of Management Diagnosis
Hypertensive crisis is defined as uncontrolled hypertension (diastolic blood pressure
≥120 mmHg and/or systolic blood pressure
≥180 mmHg) accompanied by evidence of acute end organ involvement, most commonly mani- fested by mental status changes, stroke, aortic dissection, or renal dysfunction. The initial dif- ferential diagnosis should include acute myocar- dial infarction, aortic dissection, stroke (ischemic or hemorrhagic), subarachnoid hemorrhage, renal disease, drugs (such as amphetamines, cocaine, or dietary indiscretion with MAO inhibi- tors), head trauma, and other causes of autonomic overactivity such as pheochromocytoma, auto- nomic dysfunction, or antihypertensive drug withdrawal [1].
Traditionally, fundoscopic examination is used to identify papilledema and other hallmarks of hypertension. However, few non- ophthalmologists are skilled at fundoscopic examination, and neuro-ophthalmologists only agree on the Frisen grading of 36 % of the time [2].
Fig. 15.1 Admission EKG
Optic disk diameter greater than 5 mm by ocu- lar ultrasound (Fig. 15.2) has been shown to detect intracranial pressure greater than 20 with an AUC of 0.93 [3].
The patient in this case had evidence of pul- monary edema and thus received diuretics; how- ever, many patients with hypertensive crises are volume depleted, and in the absence of obvious volume overload, diuretics should generally be avoided [5]. Renal injury from hypertensive cri- sis is manifest clinically by hematuria and creati- nine elevation. Pathologically, renal injury is described as hypertensive nephrosclerosis, with necrosis of renal capillaries and “onion skinning”
of small renal arterioles.
Withdrawal syndromes from cessation of anti- hypertensive therapy are common. Mechanisms are different depending on the discontinued med- ication. Clonidine withdrawal is seen commonly, and attributed to a rapid return of catecholamine secretion that has been suppressed during treat- ment. Symptoms from beta blocker withdrawal are related to drug half-life versus the speed of down regulation of adrenergic receptors that had
previously been up regulated due to beta- blockade. Thus, withdrawal is more commonly seen with cessation of short acting as opposed to long acting agents [6].
The diagnosis of hypertensive encephalopathy is one of exclusion. Posterior reversible encepha- lopathy syndrome (PRES) presents with head- ache, vomiting, altered mental status and seizures, with loss of gray-white differentiation and cere- bral edema, largely in the posterior portions of the brain (Fig. 15.3) [7]. While it usually resolves with treatment, there can be permanent deficits if not treated promptly.
Treatment of Hypertensive Crises
Patients with hypertensive crisis require intensive care unit admission and careful monitoring; given the usual need for parenteral treatment, an arterial line for continuous monitoring of the response to therapy should be placed in most cases. Selection of a specific agent(s) is tailored to the clinical sce- nario. Treatment goal is a reduction of systolic blood pressure by 10 % during the first hour, and 25 % during the first 24 h. In most instances the goal is not to quickly normalize the blood pres- sure, but to lower it in order to abort the crisis.
Many patients have had long-standing hyperten- sion and have auto-regulated their vasculature, and therefore a higher than normal blood pressure may be needed for adequate organ perfusion. After about 24 h of adequate control, patients are switched to an oral regimen. Management of acute aortic dissection and ischemic stroke are excep- tions to these goals (see Chapters 11 and 12).
Pharmacotherapy (Table 15.1)
(a) Esmolol as an ultra-short acting beta blocker with an almost immediate onset, and the half- life is only 9 min.
(b) Labetalol is a combined alpha- and beta- adrenergic receptor blocker with a rapid onset. It is considered safe in patients with active coronary disease because its beta- blockade does not cause reflex tachycardia.
Modified Frisen Scale
Papilledema Grade, major findings 0 (Normal)
1 (Minimal degree of edema) C shaped halo that is subtle and grayish, with a temporal gap; obscures underlying reti- nal details
2 (Low degree of edema) Circumferential halo
3 (Moderate degree of edema) Obscuration of ≥1 segment of major blood vessels leaving disc
4 (Marked degree of edema) Total obscura- tion on the disc of a segment of a major blood vessel on the disc
5 (Severe degree of edema) Obscuration of all vessels on the disc and leaving the disc Modified from Scott CJ Arch Ophthalmol 2010;128(6):705
(c) Sodium nitroprusside is a potent arteriolar vasodilator that has onset within a minute, and lasts for about 10 min. It is metabolized to cyanide and can lead to cyanide or thiocyanate
toxicity especially (but not only) when used at high doses, for periods longer than 24–48 h, or in renal insufficiency.
(d) Nitroglycerin is predominantly a venodila- tor, though intravenously at higher doses it also has arteriolar dilating effects. Its anti- hypertensive effects are less potent than nitroprusside. Prolonged use can cause methemoglobinemia.
(e) Nicardipine is a calcium channel antagonist, and is an effective drug, but it has a longer onset of action and half-life. It is used in sub- arachnoid and intracranial hemorrhage because it may reduce cerebral vasospasm, and does not increase intracranial pressure as may occur with nitroprusside.
(f) Hydralazine as a direct arteriolar dilator. It can cause reflex tachycardia. Its use is generally limited to pregnant women who cannot use other agents.
(g) Less commonly used agents:
• Clevidipine is a short acting dihydropyri- dine calcium channel blocker, with an elimination time of between 5 and 15 min.
It is an arteriolar dilator, and it is adminis- tered in a lipid emulsion, and is contrain- dicated in patients with allergies to eggs or soy products [9].
Fig. 15.3 Axial flair image of MRI of patient with PRES, demonstrating high signal activity (arrow) confined to the white matter in a posterior distribution (Image courtesy of Barton F Branstetter IV, MD)
Fig. 15.2 Ocular ultra- sound with optic nerve measurement 3 mm poste- rior to retina arrows indi- cate edges of the optic nerve (Image courtesy of Phil Lamberty, MD)
Table 15.1Drugs used for the treatment of hypertensive crises DrugDoseOnsetDurationRoleContraindications and CaveatsAdverse effectsCost/Day Sodium nitroprusside0.25 μg/kg/min to max of 8 μg/kg/minSeconds1–2 min after stoppingAortic dissection (in conjunction with beta-blocker), hyperadrenergic conditions, encephalopathy Avoid with CVA, ICH, SAH. Caution in renal insufficiency – rates >4 μg/kg/min can cause toxic levels in 3 h (15) Nausea, cyanate & thiocyanate toxicity, increased intracranial pressure, decreased cerebral blood flow, coronary steal
$12–$252 Nitroglycerine5 μg/min titrate by 5 μg/min every 15 min to max of 100 μg/min
2–5 min5–10 minCardiac ischemia, CHF, hyperadrenergic states, encephalopathy, renal failure
Concurrent use PDE-5 inhibitors. NTG is mostly a venodilator until high doses, care in patients who are volume depleted, tachyphylaxis common
Decreased CO headache, dizziness$4–$12 Nicardipine5 mg/h increase by 2.5 mg increments q 20 min to max of 15 mg/h
5–10 min2–4 hAortic dissection in conjunction with beta blocker, cardiac ischemia, stroke, CNS bleed, hyperadrenergic conditions, encephalopathy, renal failure Tachyphylaxis, avoid calcium channel blockers in CHF
Headache, flushing, nausea, reflex tachycardia, edema
$87–$262 Clevidipine1–2 mg/h double every 90 s to max of 16 mg/h
2–4 min5–20 minConjunction with beta blocker, CHF, cardiac ischemia, stroke, CNS bleed, hyperadrenergic conditions, encephalopathy, renal failure Egg or soy allergyHeadache, flushing, nausea, reflex tachycardia
$260–$1300 Fenoldopam0.1–0.6 μg/kg/min titrate q15 min5–10 min10–15 minRenal failure aortic dissection in conjunction with beta blocker
GlaucomaHypotension, headache, tachycardia, nausea, flushing
$163–$985 (continued)
Table 15.1(continued) DrugDoseOnsetDurationRoleContraindications and CaveatsAdverse effectsCost/Day Labetolol20 mg bolus; repeat boluses of 20–80 mg q10 min or 2 mg/min drip to total of 300 mg/day 5–10 min3–6 hMyocardial ischemia; hyperadrenergic states, aortic dissection, encephalopathy
Bradycardia, heart block, bronchospasm$276 Esmolol50 μg/kg load over 1 min; infusion at 20–50 μg/kg/min titrate by 25 μg/kg/ min q 10 min to max of 300 μg/kg/min
1–5 min15–30 minMyocardia ischemia, hyperadrenergic states, aortic dissection, encephalopathy
Bradycardia, heart block, bronchospasm$1270– $19,501 Enalaprilat1.25 mg over 5 min titrate by 1.25 mg increments q12 h to max of 5 mg q6 h
15 min4–6 hCaution with renal insufficiencyRenal insufficiency, hyperkalemia. Unpredictable results depending on plasma renin levels
$5–$20 Phentolamine5–10 mg repeat q5–15 min or drip at 0.2–5 mg/min
1–2 min5–10 minAdrenergic crisisReflex tachycardia, headache, nausea$6902– $172,000 Hydralazine10–20 mg bolus q30 min until target BP reached 10 min2–6 hPregnancyReflex tachycardia results inconsistent prolonged effect
$25 Costs are as of 2015 in a single teaching hospital
• Fenoldopam as a dopamine agonist, and is the only intravenous agent that increases renal blood flow. It can increase intraocu- lar pressure so should not be used in patients with glaucoma [10].
• Phentolamine is a nonselective alpha- adrenergic receptor blocker, and its use is largely in patients with pheochromo- cytoma or tyramine ingestion in patients who are on monoamine oxidase inhibi- tors. In these latter instances, one should not use beta-blockers until suf- ficient alpha blockade has been achieved; doing so could remove the vasodilatation of beta-1 stimulation, making the alpha mediated constriction worse.
• Enalaprilit is an intravenous form of enal- april. The blood pressure response to this agent can be variable because its action is dependent on plasma volume and renin activity. If the patient is hypovolemic with high plasma renin, excessive hypotension has been reported.
(h) Suggested drugs for specific clinical scenar- ios are shown in Table 15.2.
Evaluation for Secondary Causes of Hypertension
The prevalence of secondary hypertension is higher in patients who have presented with a hypertensive crisis compared with those who have not. Evaluation should be considered as guided by clinical presentation. Ten to forty-five percent of patients with hypertensive crises have renal artery stenosis [11]. Common secondary causes and suggested diagnostic strategies are outlined in Table 15.3.
Treatment of cocaine-induced hypertension includes benzodiazepines to reduce the central stimulatory effects of the cocaine, calcium antagonists, alpha blockers, and either nitroglyc- erin, nitroprusside, or clevidipine. Beta blockers are generally avoided because of the risk of removing beta-1 mediated vasodilation [12].
Evidence Contour
There are few high quality studies comparing various treatment modalities and outcomes for hypertensive crises. Those studies that are avail-
Table 15.2 Suggested drugs in particular clinical scenarios
Clinical scenario Suggested drugs
Cardiac ischemia Nitroglycerin, nitroprusside, or nicardipine plus a beta blocker such as esmolol, labetalol, or metoprolol
Pulmonary edema/congestive heart failure Nitroglycerin, nitroprusside, or clevidipine; add beta blocker if tachycardic
Aortic dissection Nitroprusside, clevidipine, or fenoldopam plus beta blocker such as labetalol or esmolol
Renal dysfunction (hematuria or worsening creatinine)
Fenolodopam [16]
Catecholamine excess (pheochromocytoma, drug withdrawal, cocaine, amphetamines)
Nicardipine, clevidipine, nitroprusside; benzodiazepines for cocaine
Hypertensive encephalopathy Nicardipine, clevidipine, fenoldopam Ischemic stroke (if BP >220/120 if not receiving
thrombolytics, or >185/110 if receiving thrombolytics)
Nicardipine, clevidipine, fenoldopam
Intracerebral hemorrhage (if BP >200 or mean
>150)
Nimodopine, nicardipine, clevidipine, fenoldopam Subarachnoid hemorrhage (if BP >160) Labetalol, nicardipine, clevidipine plus PO nimodopine for
spasm reduction
Pregnancy (>150/100) Labetalol, hydralazine, nitroglycerine if associated pulmonary edema
able generally are observational, demonstrating the ability of an agent to achieve target blood pressures in what timeframe, or comparing a newer drug with an established agent, (e.g., clevi- dipine versus nitroprusside, or nicardipine with labetalol); in general, they demonstrate that all agents described in this chapter have utility in appropriate circumstances, without clear superi- ority of one versus another.
Specific Subsets of Patients
with Hypertensive Crisis May Warrant Specific Treatment Approaches
(a) Blood pressure control for acute neurologic syndromes. As discussed above, recom- mended target blood pressures vary in differ- ent neurologic syndromes, and clear guidance is not available for any of them (see Chapter 34) [8, 13].
(b) The use of beta blockers in cocaine intoxica- tion is unclear. The concern is that beta- blockade removes the beta mediated vasodilatation and thus can make the hyper- tension worse, and can make vasospasm worse. Given the significant recidivism rate, having patients on chronic beta-blockade may be unwise. However, in the presence of LV dysfunction or significant arrhythmias, the benefits may outweigh the risk, and at least one study raises the possibility that beta-blockers are not detrimental [14]. In
general, however, most physicians avoid beta blockers.
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Cause Screening test Definitive test
Chronic renal disease UA/creatinine/renal ultrasound
Renovascular disease Duplex Doppler MRI, CT angiography
Coarctation of aorta BP arms and legs Echo, MRI, CT angiography
Primary aldosteronism Plasma and urinaryK Plasma aldosterone/renin ratio
Urinary aldosterone after salt load; adrenal CT; adrenal vein sampling
Cushing’s disease Dexamethasone suppression
Pheochromocytoma Plasma free metanephrines
Urine metanephrines, catecholamines (falsely elevated during stress)
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