Hypertensive emergencies
1. Introduction
The severest hypertensive states pose an immediate threat to life. To be able to manage these situations, physicians need well-defined recommendations; however, as with some other emergencies, only few evidence-based strategies have been developed to date.[1] As randomized, placebo-controlled trials are very difficult to design and conduct, most guidelines and recommendations are based just on experience. The recommendations and opinions in the present chapter draw mainly from national, European, and American guidelines for the treatment of hypertension, and on guidelines of professional societies such as the European Stroke Organisation as well as the experience gained in the author´s health-care center.[2-6]
2. Terminology
The terminology used for severe hypertensive states is not fully consistent, clear, and systematic. Severe hypertension-associated states can be divided into
According to the guidelines of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC),
3. Etiology and prevalence of hypertensive emergencies
A role in the etiology of emergent hypertensive states is most often played by inadequate treatment of known hypertension and therapy discontinuation. [2,3,7] Pathophysiological mechanisms include a sudden rise in peripheral vascular resistance and systemic vasoconstriction due to activation of the renin-angiontension-aldosterone system, sympathoadrenal system, endothelin, exogenous factors, injury to the central nervous system, bleeding, tumor or ischemia, or perioperative stress. Except for conditions associated with renal failure, increased natriuresis and vasoconstriction result in reduced vascular filling. This can be effectively managed by afterload reduction; diuretic use is less effective. Hypertensive encephalopathy develops due to cerebral edema, which forms once the autoregulatory capacity of blood flow through brain arteries has been exceeded. The autoregulatory threshold is typically a mean BP of 140 mm Hg; however, the value may be higher in protracted severe hypertension. Other factors contributing to the development of edema include both hydrostatic mechanisms and changes in the vascular wall.[8]
The exact prevalence of severe hypertensive states is not known. These states occur more frequently in patients with nephrogenic hypertension and hyperaldosteronism. An emergent hypertensive status develops in about 1% of hypertensives during their lifetime.[9] An earlier US study reported about 8% and 16% of patients presenting at medical part of the emergency department with emergent and urgent hypertensive states, respectively.[10] In the experience of the author of this chapter, about 5% of patients admitted to the Intensive Cardiac Care Unit are diagnosed to have states somehow related to severe hypertension.
4. Clinical picture
The most frequent complaints accompanying HE include chest pain (27%), dyspnea (22%), headache (22%), epistaxis (17%), weakness and psychomotorical agitation (10%), whereas other authors list headache (49%) and weakness (22%) as the most frequently experienced problems.[5,8] Other complaints include palpitations, nausea, vomiting, anxiety and feeling of illness. Organ damage manifests itself most often as cerebral stroke (24%), lung edema (23%), neurological deficit (21%), and hypertensive encephalopathy (16%). Cerebral hemorrhage is diagnosed as little as 4.5% of cases (Tab. 2).[10] Retinal hemorrhage, exudates, and papilledema can also occur, indicating damage to other organs. These lesions do not subside until after several weeks since BP reduction. Oliguria, hyperazotemia, and proteinuria signal renal injury. Patients complaining of concomitant chest pain or other discomfort or with EKG-documented ST-segment depressions and a mild increase in cardiac troponins in serum can be diagnosed, according to the Universal definition of myocardial infarction, as type 2 myocardial infarction due to an imbalance between oxygen demand and supply.[11]
5. Examinations
Given the possibility of coarctation, atheorsclerosis of brachial arteries or, possibly, aortic dissection, BP should be measured on both arms. Measurement of BP in the lower limbs will rule out stenosis of arteries in both arms, a rare occurence. Blood pressure is measured using a properly-sized cuff to match the limb circumference. During subsequent managements in the ICU, BP is commonly measured noninvasively at intervals of 5 minutes to 1 hour depending on the severity of organ damage and BP level and instability. Only in cases of persisting instability of BP and its difficult control, or with conditions such as dissecting aneurysm requiring controlled hypotension, is it necessary to insert an arterial line. The cannula should be preferably inserted after a reduction of BP by initial therapy in some compressible brachial artery. An integral part of physical examination is neurological assessment to guide therapy. Basic biochemical tests including plasma concentration of minerals, urea, creatinine, markers of myocardial necrosis, natriuretic peptides, liver tests (to determine elimination of drugs), urinalysis (albuminuria, hematuria, crystaluria, etc.), and blood count should be done immediately. Additional examinations include EKG, chest x-ray, and fundoscopy. Echocardiography is performed in the context of hypertension primarily to assess the presence of myocardial dysfunction, muscle hypertrophy or, possibly, to roule out dissection of the aorta. Patient diagnosed to have focal neurological deficit and encephalopathy require a brain CT. Additional examinations are performed based on the patient´s current status.
6. Management
7. Drugs for IV therapy of severe hypertension
The agents currently available for parenteral therapy include nitrates, urapidil, diuretics, angiotensin-converting blockers, calcium-channel blockers, beta-blockers, alpha-blockers, combined alpha-and beta-blockers, clonidine and fenoldopam.(Tab. 3) [2,3,6]
In the case of perioperative hypertension, the recommendation is to initiate therapy with a 25 mg bolus; if effective within 2 minutes of the initial bolus, the patient can be switched to maintenance therapy. The recommended dose of urapidil for maintenance perioperative therapy is 60-180 mg/hour. No data regarding gestational hypertension and urapidil excretion to breast milk are currently available.[14-19]
As urapidil has not yet been approved by the US Food and Drug Administration (FDA), it is simply not mentioned in a number of texts published in the USA.
Labetalol is both a selective alpha1-blocker and predominantly a non-selective beta-blocker. Treatment is initiated depending on its effect with 5-160 mg boluses administered repeatedly at 2-10 minutes to a maximum dose of 300 mg. Labetalol can also be administered continuously at a rate 2 mg/minutes up to a total dose of 300 mg/24 hours. The effect sets in within 5-10 minutes and resolves within 2-6 hours. A traditional indication-apparently based, in particular, on the absence of adverse experience-is management of pre-eclampsia/eclampsia. It is also the drug of choice in other situations, except those contraindicated to beta-blocker use.[32] In the USA, labetalol is the drug most often used in the treatment of HE.
8. Management in specific situations
The choice of individual classes of drugs depends on the underlying disease resulting in HE or it is associated with. To date, only few randomized studies have been conducted evaluating treatment of HE and almost no studies designed for head-to-head comparison of various drugs.[1]
In
In
In
In
In
Treatment of
In
In
9. Prognosis
Uncontrolled malignant hypertension results in 90% one-year mortality due to heart failure, stroke, or renal failure. There are virtually no data from randomized controlled studies showing how treatment with individual drugs affects mortality and morbidity, and whether any drug is superior to another one. Introduction of novel ultrashort-acting and well tolerated drug are expected to provide the greatest benefit in the near future.
Hypertensive encephalopathy |
Hypertension with heart failure |
Hypertension in acute coronary syndromes |
Hypertension in aortic dissection |
Hypertension in intracranial hemorrhage Hypertension in ischemic stroke |
Sympathetic crises due to pheochromocytoma |
Sympathetic crises after abuse of so-called recreational drugs (amphetamine, LSD, cocaine, ecstasy/MDMA) |
Perioperave hypertension |
Eclampsia and severe pre-eclampsia |
Acute renal failure in hypertension |
Table 1.
|
% |
Chest pain | 27 |
Dyspnea | 22 |
Headache | 22-40 |
Nosebleed | 17 |
Weakness and psychomotor agitation | 10-22 |
|
|
Increase in troponin levels above the diagnostic cut-off for AMI (Type-2 AMI) | 38 |
Stroke | 24 |
Pulmonary edema | 23 |
Neurological deficit | 21 |
Hypertensive encephalopathy | 16 |
Cerebral hemorrhage | 4.5 |
Table 2.
Most common manifestations of emergent and urgent hypertensive states
|
Mechanism of action: venodilatation, at higher doses arteriodilation |
Onset of action: maximal effect within 2-5 minutes |
Duration of action: 5-10 minutes |
Specific indications: medication of choice in almost all situations, mostly first choice medication, advantageous especially for heart failure and acute coronary syndromes |
Specific contraindications: ischemic stroke |
|
Mechanism of action: arterio- as well as venodilation |
Onset of action: almost immediate, maximal effect within 2-3 minutes |
Duration of action: minutes, circulatory half-life about 2 minutes |
Specific indications: particularly resistant hypertension, controlled hypotension |
Specific contraindications: liver failure, severe cardiovascular stenotic defects, ischemic stroke |
|
Mechanism of action: vasodilatation (antagonist of peripheral alpha1-postsynaptic receptors, antagonist of central 5-hydroxytryptamine-1A receptors), mild beta1-blockade |
Onset of action: almost immediate, maximal effect within 2-5 minutes |
Duration of action: up to 4 hours |
Specific indications: sever and resistant hypertension in almost all situations, controlled hypotension |
Specific contraindications: no data regarding lactation |
|
Mechanism of action: vasodilatation (centrally acting alpha2-agonist), sedative, analgesic and opioid |
properties |
Onset of action: almost immediate |
Duration of action: plasma half-life is ranging between 10 and 20 hours |
Specific indications: for combinations in resistant hypertension and situations requiring sedative effect |
Specific contraindications: severe brady-arrhythmias resulting from either sick sinus syndrome or AV block of 2nd or 3rd degree |
|
Mechanism of action: selective renal dopamine D1 receptor agonist; renal, mesenteric and coronary arteriodilation, increase of sodium excretion |
Onset of action: rapid, most of the antihypertensive effect attained in 15 minutes |
Duration of action: quickly reversible, half-life 5-10 minutes |
Specific indications: particularly useful in patients with severe hypertension associated with end-organ renal damage or volume overload |
Specific contraindications: administration with beta-blockers |
|
Mechanisms of action: angiotensin-converting enzyme, normalization of cerebral vascular autoregulation |
Onset of action: within 15 minutes, peak effect after 1-4 hours |
Duration of action: 6 - 24 hours |
Specific indications: drug of two to third choice in resistant hypertension |
Specific contraindication: pregnancy, common contraindications to angiotensin-converting enzyme inhibitors |
|
Mechanisms of action: calcium-channel blocker with preferential activity on cerebral vessels; increase of cerebral perfusion, particularly in poorly perfused areas, by arterial dilatation |
Onset of action: almost immediate |
Duration of action: the half-life is 1.1 - 1.7 hours, the terminal half-life is 5-10 hours |
Specific indications: preferably aneurysmal subarachnoidal hemorrhage |
Specific contraindication: lack of a central venous catheter |
|
Mechanisms of action: calcium-channel blocker; selective arteriolodilatation including coronary arteries |
Onset of action: within 2–4 min. |
Duration of action: 5–15 min. |
Specific indications: rapid reduction of BP in the perioperative setting |
Specific contraindication: must not be used in patients with defective lipid metabolism accompanied by hyperlipidemia. |
|
Mechanisms of action: calcium-channel blocker; decrease in peripheral vascular resistance, without an increase in heart rate as a reflex response |
Onset of action: within 5 min. |
Duration of action: half-life between 3.5 and 7.4 hours |
Specific indications: hypertension with tachycardia and contraindications to beta-blockers |
Specific contraindication: common to calcium-channel blockers |
|
Mechanisms of action: beta1-selective blocker |
Onset of action: maximal effect of the selected dose within 5 min. after bolus |
Duration of action: 10-30 min., half-life 9 min. |
Specific indications: perioperative hypertension, aortic dissection, ischemic stroke, acute coronary syndrome |
Specific contraindication: pregnancy, common contraindications to beta-blockers |
|
Mechanisms of action: selective beta-blocker |
Onset of action: within 5 min. |
Duration of action: to 4 hours, elimination half-life 1-9 hours, average 3.5 hours |
Specific indications: aortic dissection, acute coronary syndrome |
Specific contraindication: pregnancy, common contraindications to beta-blockers |
|
Mechanisms of action: non-selective beta-blocker, weak alpha-blocker |
Onset of action: within 5-10 min. |
Duration of action: 2-6 hours |
Specific indications: eclampsia, any severe hypertension |
Specific contraindication: common contraindications to beta-blockers |
|
Mechanisms of action: non-selective alpha-blocker |
Onset of action: minutes |
Duration of action: 2-4 hours |
Specific indications: during surgical manipulation with phaeochromocytoma |
Specific contraindication: common contraindications to alpha-blockers |
Table 3.
Medication for the management of hypertensive emergencies
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