Approaches to Emergency Department Care

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Training REVIEW ARTICLE accredited Hypertension, hypertensive crisis, and hypertensive emergency: approaches to emergency department care

ELISENDA GÓMEZ ANGELATS, ERNESTO BRAGULAT BAUR Sección de Urgencias Medicina. Área de Urgencias. Hospital Clínic. Barcelona, Spain.

CORRESPONDENCE: Elevated arterial blood pressure is a frequent reason for seeking emergency care. It is Dra. Elisenda Gómez Angelats important to remember that pressure elevation alone does not define whether the Sección de Urgencias Medicina situation should be considered a life-threatening emergency or denotes only a need for Área de Urgencias urgent attention. Rather, it is the signs and symptoms accompanying the elevation that Hospital Clínic will reveal which patients are in need of emergency treatment. A hypertensive emergency C/Villarroel, 170 is characterized by clear signs of acute injury to a target organ, presenting as hypertensive 08036 Barcelona. Spain encephalopathy, intracranial bleeding, acute coronary syndrome, heart failure with acute E-mail: [email protected] pulmonary edema, aortic dissection, eclampsia or preeclampsia, or accelerated RECEIVED: hypertension. These situations require the immediate but not abrupt reduction of arterial 17-6-2009 pressures by means of parenteral administration of drugs. A hypertensive patient in need of urgent care, but not in an emergency situation, on the other hand, has seriously ACCEPTED: elevated pressures but no signs of acute or progressive target organ injury. Such a patient 29-9-2009 requires gradual reduction of pressures over a period of 24 hours to several days and can receive oral treatment. A large number of drugs are available for managing hypertension. CONFLICT OF INTEREST: No single drug has been reliably shown to be better than others at reducing pressures, None whether administered parenterally or not. However, recommendations can be made based on the accompanying clinical picture and individual patient characteristics. This review will outline such recommendations. [Emergencias 2010;22:209-219]

Key words: Hypertension. Hypertensive crisis. Hypertensive emergency.

Introduction rapid and optimal BP control, and the new criteria for treatment based primarily on pathophysiologi- Hypertensive crises are a frequent cause of cal mechanisms causing BP elevation. emergency department (ED) visits. An isolated reading of blood pressure (BP) alone does not define the clinical picture as a hypertensive crisis. In Definitions other words, there are many clinical situations that are accompanied by an elevation of BP, A hypertensive crisis is considered to be any in- which may generate confusion as to whether high crease of BP generally above 180/120 mmHg. De- BP (hypertension: HT) in a particular context is pending on the magnitude and the presence or the cause or the consequence of the picture giv- absence of target organ damage (TOD) and the ing rise to the visit. Although hypertensive crises presence of associated symptoms, it is subdivided usually occur in HT patients who are untreated or into HT emergency (life-threatening), urgent at- inadequately treated, its definition and clinical tention HT or pseudocrisis2. course should not be confined to the magnitude of the rise in BP value, but also the existence of Hypertensive emergency specific clinical symptoms that will be discussed below. Similarly, it should be noted that moder- This refers to intense elevation of BP associated ately high BP values can lead to emergency situa- with acute injury to vulnerable organs. Pro- tions in a previously normotensive person1. nounced increases in BP accompanied by obvious In this review we discuss those emergency situ- TOD should be treated immediately (without nec- ations that require special treatment to achieve essarily waiting for high values to return to nor-

Emergencias 2010; 22: 209-219 209 E. Gómez Angelats et al.

mal BP) to prevent or limit organ damage3. Exam- tient with nephritic colic and BP 180/120 mmHg ples of hypertensive emergencies: hypertensive constitutes hypertensive emergency with renal im- encephalopathy, intracranial hemorrhage, acute pairment. Conversely, a patient with rapidly pro- coronary syndrome (ACS), heart failure with acute gressive dyspnea and BP 150/105 mmHg consti- pulmonary edema, dissecting aorta, eclampsia- tutes a hypertensive emergency with cardiac eclampsia and accelerated hypertension. A patient involvement and acute lung edema, which re- with a hypertensive emergency usually presents quires immediate lowering of BP. It is therefore grade III-IV retinopathy. It is therefore a process very important to assess the patient's clinical con- that is identified by the symptoms experienced by text when classifying cases as hypertensive crisis or the patient and not by the values of BP. urgent attention HT, since the approach and therapeutic implications are going to be very different. Urgent attention HT It should also be noted that patients with chronic hypertension may tolerate BP levels of This denotes elevated BP not accompanied by 150/100 mmHg well and without symptoms, progressive TOD, and therefore requires gradual while the same levels in younger patients with normalization of BP values in a period of time acute glomerulonephritis, or after cocaine con- ranging from 24 hours to several days with orally sumption, may generate severe symptoms. administered drugs. It is therefore important to In the case of a possible hypertensive emer- note that the difference between urgent attention gency, the symptoms and physical findings guide HT and hypertensive emergency is not in the val- us to the diagnosis. Thus, a patient may consult ues of BP but rather the existence of TOD. Thus, for visual disturbances, headache, confusion and patients with long-standing HT may have diastolic vomiting as a manifestation of hypertensive en- BP between 120-140 mmHg and be asympto- cephalopathy or with reduced level of conscious- matic, while patients with preeclampsia, cocaine ness in the case of intracerebral hematoma or users or patients with acute glomerulonephritis subarachnoid hemorrhage. presenting DHT of 105-110 mmHg may consti- Cardiovascular disorders include ACS, rapidly tute a hypertensive emergency. progressive dyspnea in the case of acute pulmonary edema and chest pain and/or abdominal Hypertensive pseudocrisis or false hypertensive pain in the case of aortic dissection. crisis In the case of pregnant women with preeclampsia, the appearance of severe renal im- This refers to transient elevation of BP appear- pairment with oliguria, anuria and microangio- ing in different situations and diseases, and BP el- pathic anemia indicates eclampsia (Table 1). evation is a secondary phenomenon associated The most common presentation of accelerat- with them. We may see this in situations of pain, ed-malignant hypertension is headache with visual emotional stress, peripheral vertigo, spinal cord alterations, which appear in up to 50% of pa- injury, acute urinary retention, hypoxia, brain tients with this type of hypertensive emergency4. damage with intracranial hypertension, etc. In It is characterized pathologically by fibrinoid these cases the treatment should be directed to- necrosis of the arterioles and myointimal prolifera- ward the underlying disease, since the BP values tion of small arteries, manifesting in the form of usually normalize once the cause of elevation is retinopathy (hypertensive grade III-IV) and renal resolved. disease evidenced by impaired renal function and/or hematuria and/or proteinuria. The patient requiring urgent attention for hy- Clinical Manifestations pertension is one who, despite high BP, does not exhibit any BP-related symptoms, as shown in There are many and varied main reasons for ED Table 1. visits or referral among patients with a “HT crisis”. They range from the asymptomatic patient referred after an incidental finding of high BP to a Initial assessment patient with acute pulmonary edema. As men- tioned, BP values per se do not determine case Patients attending an emergency department severity, but the accompanying symptoms do, in for elevated BP are usually referred or attend which case severity depends on the target organ spontaneously due to the appearance of a symp- affected. However, this does not mean that a pa- tom accompanied by the elevation. So, initially,

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Table 1. Main forms of presentation of hypertensive emergencies in the emergency department Hypertensive emergencies Symptoms Hypertensive encephalopathy Headache, visual disturbances, vomiting, altered level of consciousness. Severe hypertension with ischemic stroke/cerebral hemorrhage Neurological deficit, altered level of consciousness. Hypertensive left ventricular failure Cough, dyspnea, orthopnea, rapidly progressive dyspnea. Accelerated-malignant hypertension Visual changes, headache. Renal failure, oliguria, hematuria. Hypertension and aortic dissection Chest pain and/or intense abdominal pain. Vegetatism, signs of poor perfusion. Hypertension with acute coronary syndrome Chest pain. Use of drugs such as amphetamines, LSD, cocaine or ecstasy Tachycardia, sweating, altered mood and / or level of consciousness. Severe preeclampsia or eclampsia Oliguria, anuria, microangiopathic anemia. rapid triage should assess whether this elevation tion and an emergency, with a view to establish- involves the possibility of TOD, at least incipient, ing the most appropriate diagnostic and thera- and therefore makes the case a hypertensive peutic strategy. emergency. It is important to establish whether the patient is known to be hypertensive or not, the regular medication and adherence to treat- Are complementary tests necessary ment, as well as their usual BP values. Many pain the asymptomatic patient? tients with chronic hypertension have BP values which range between 150/90-100 mmHg and are This is often asked in the ED. A proper history asymptomatic. It is also important, especially in and complete physical examination, including younger people, to inquire about the possibility of fundus examination, can allow one to detect signs drug use, such as amphetamines or cocaine. It is and symptoms of TOD that were initially not ap- also important to collect information about possi- parent. Thus, in asymptomatic patients, one may ble consumption of medication such as ergot, detect grade III-IV retinopathy, or the patient may non-steroidal anti-inflammatory agents, nasal de- present mild confusion, previously not known, congestants, and failure to adhere to normal hy- dyspnea or oliguria. The performance of comple- pertensive medication or abrupt termination of mentary tests in a patient attending for BP eleva- beta-blockers. tion should be evaluated individually, taking into BP must be measured in both arms, if possible, account the patient’s symptoms and clinical find- and take into account that in obese patients the ings. use of BP arm bands that are not adapted to the In a recent study6, an electrocardiogram and a arm circumference causes falsely high readings4. chest radiograph changed the diagnostic and Relevant information should include BP values therapeutic decision in only 2 out of 116 patients, before the ED visit, previous or only current caus- and the authors concluded that it is not necessary es for concern, and prescribed medication being to perform such additional examinations in this taken. type of patients if they show no symptoms sug- The physical examination should focus on gestive of TOD. identifying or excluding evidence of acute TOD. It Generally, in all patients with symptoms and/or is important to check peripheral pulse symmetry. signs of hypertensive emergency, and while treat- Auscultation of crackles in a dyspneic patient with ment is initiated, the following are necessary: orthopnea and cough as an atypical symptom complete blood count and biochemistry, urine should arouse suspicion of acute lung edema, and strip test for proteinuria, and electrocardiogram the presence of angina suggests ACS. A neurolog- that will help detect signs of left ventricular hy- ical deficit is suggestive of either ischemic or hem- pertrophy and electrical changes in case of chest orrhagic stroke, and not hypertensive en- pain, as well as chest X-ray to assess the medi- cephalopathy, which manifests in the form of astinum, the cardiothoracic ratio and signs of headache and altered level of consciousness. Fundus examination, mandatory in all hyper- Table 2. Keith-Wagener-Barker classification of hypotensive tensive crises, may reveal the presence of exudate retinal changes and hemorrhage (grade III retinopathy), and/or Grade I Mild generalized retinal arteriolar narrowing. papilledema (grade IV retinopathy), in which case Grade II Definite focal narrowing and aretriovenous nipping. the rise in BP should be treated as a hypertensive Grade III The above and retinal hemorrhages, exudates, and cotton wool spots. Many of these patients present cardiac, brain emergency (Table 2). or kidney compromise. Based on this assessment we should be able to Grade IV Severe grade III and papilloedema. Cardiac, brain and distinguish between cases requiring urgent atten- kidney compromise is more severe.

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heart failure. In addition, we should proceed to 70 determine troponin I levels in cases of suspected 60 ACS or heart failure. 50

In hypertensive emergency patients with neu- 40 rological deficit or altered level of consciousness, 30 Normotensive CT scan should be requested. Suspected aortic 20 dissection must be confirmed by contrast CT scan Hypertensive 10 or chest MRI. If accelerated BP is suspected, schis- 0 tocyte count must be requested to rule out mi- 0 25 50 75 100 125 150 175 200 croangiopathic hemolytic anemia. Figure 1. Diagram showing the limits of cerebral blood flow self-regulation in relation to changes in blood pressure. X axis: cerebral blood flow (ml/100 g per min) and Y axis: values of Considerations in the initial management blood pressure in mmHg (Adapted from Strangaard et al, Br of PA Med J.).

The asymptomatic patient fast reduction is associated with complications such as cerebral, myocardial or renal hypoperfu- To date, no studies clearly demonstrate the sion2. That is why the management of these pa- most appropriate ED approach to the asympto- tients is based on the use of easily titrated drugs matic patient with a hypertensive crisis. Despite with short half-life in continuous infusion. For the this lack of evidence, it is very common for the at- same reason, the sublingual and intramuscular in- tending physician to choose to initiate treatment jection routes should be avoided. in the ED6. In this case, and before starting, we In a hypertensive emergency, the immediate ob- should be aware that at least one third of patients jective is to reduce DBP by 10-15% or to 110 with DBP increase >95 mmHg in the ED show mmHg over a period of 30 to 60 minutes. In pa- spontaneous decrease before they begin follow tients with suspected or confirmed aortic dissection, up7. BP elevation in the absence of symptoms or the BP must be reduced quickly, in 5-10 min, until signs of TOD rarely requires urgent treatment but achieving and SBP <120 mmHg, as tolerated10,11. does require deferred monitoring/treatment3,4. Once BP has been controlled and accompany- Most patients attending the emergency depart- ing organ damage has ceased, oral antihyperten- ment with elevated BP do not present acute TOD sive drugs should be started, and the dose of the in the initial evaluation. They are usually patients continuous infusion progressively reduced. attending for many different diseases, and therefore the elevated BP should be evaluated in the context of chronic hypertension. In these patients, Drugs used in hypertensive crises either because the finding is coincidental or because they are asymptomatic and without evi- Habitually, intravenous drugs are used in hyper- dence of acute TOD, treatment should be aimed tensive emergencies and oral drugs in cases of ur- at achieving a progressive decrease in BP with oral gent attention12. A great variety of antihypertensive drugs within 24-48 hours8, and it is not recom- agents are used in hypertensive crisis. The choice mended that one should wait for BP values to nor- of drug depends on the patient's clinical condition malize "pharmacologically" in the ED itself. Rapid and symptom presentation. The most commonly BP reduction, especially in patients with chronic used in emergencies are: labetalol, fenoldopam, hypertension, is accompanied by a shift to the nitroglycerin and nitroprusside, because they are right in the selfregulation pressure/perfusion curve easily titratable, and their effect is rapid. (Figure 1), in the brain, heart and kidney9, which may lead to cerebral, myocardial or renal ischemia Cases requiring urgent attention and infarction, respectively, so this approach is formally disallowed in hypertensive emergencies. It is important to remember that sublingual nifedipine is not recommended in any type of hy- Hypertensive emergency pertensive crisis3. The recommended drugs are those with long half-life (Table 3), since the aim is Given that hypertensive emergency patients to normalize BP values in about 48-72 hours3. An- present TOD, a rapid but controlled correction of giotensin converting enzyme inhibitors (ACEI) are BP is necessary. It should be noted that extremely most commonly used in cases requiring urgent at-

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Table 3. Main drugs used in the treatment of hypertensive Hypertensive Emergencies patients requiring urgent attention Drug Initial Dose Labetalol

Calcium antagonists (long-acting dihydropyridines) This is a combined selective blocker of α1 Amlodipine 5-10 mg and non-selective blocker of β-adrenergic recep- Lacidipine 4 mg tors, with an - blocker ratio of 1:7. Its hy- Betablockers α β Bisoprolol 2,5-5 mg potensive action begins at 2-5 minutes after in- Carvedilol 12,5-25 mg travenous administration, reaching a peak at Atenolol 25-50 mg 5-15 minutes, with a duration of between 2 and Diuretics 14 Furosemide 20-40 mg 4 hours . Unlike selective beta-blockers, it does Torasemide 5-10 mg not have a negative inotropic effect15. It decreas- Angiotensin-converting enzyme inhibitors es peripheral resistance without reducing pe- Captopril 12,5-25 mg Enalapril 5-20 mg ripheral flow, whereas renal, cerebral and coro- Angiotensin II receptor antagonists nary blood flow remain constant. It can be used Losartan 50 mg in cases of eclampsia and preeclampsia because Irbesartan 75-150 mg Candesartan 8-16 mg passage through the placental barrier is Alpha blockers minimal15-18. Doxazosin 1-4 mg It is administered with an initial loading dose of 20 mg, followed by progreesively larger doses of 20 to 80 mg in 10 minute intervals. After the tention, especially captopril, which has faster on- loading dose, one can start infusion of 1-2 set of action (between 30 and 60 minutes)13, al- mg/min titrated on the basis of the hypotensive though, as said, BP should not be reduced too effect desired. A bolus of 1-2 mg/kg should be rapidly. Any drug with a relatively fast onset of ac- avoided because of the risk of sudden hypoten- tion can be used, including loop diuretics, β- sion (Table 4). blockers, α2-adrenergic agonists or calcium antagonists (except short-acting nifedipine). The most Esmolol significant change in recent years in pharmaco- This is a cardioselective blocker with extremely logic management of hypertension has been the short-acting effect. Onset of action occurs in 1 development of type 1 angiotensin II receptor an- minute, with a duration of 10-20 minutes. A bolus tagonists (ARA II), of which Losartan is the most of 0.5 mg/kg is recommended followed by con- used. The use of these drugs in hypertensive tinuous infusion of 25-300 mg/kg/min. This drug crises is poorly documented but possibly the de- is safe in ischemic heart disease, and given its crease in BP is comparable to that obtained with pharmacokinetic properties, some authors consid- ACE inhibitors, although the onset of its action er it to be the beta-blocker of choice in critically may be slower. ill patients19 (Table 4).

Table 4. Major drugs administered for the treatment of hypertensive emergency Drug Mechanism Dosage Effect Duration Specific indications Labetalol α-β-blocker Bolus 20 mg and repeat bolus with doses 5-10 min 3-6 h Most hypertensive (not cardioselective) of 20-80 mg at 10 min intervals emergencies. (Max. 300 mg) Stroke. Perfusion: 1-2 mg/min Esmolol β-blocker Bolus 0,5 mg/Kg 1-2 min 10-20 min ACS. (cardioselective) Perfusion 25-300 µg/Kg/min Enalapril ACEI Bolus de 1 mg 15-60 min 4-6 h Hypertensive encephalopathy. Fenoldopam Dopamine agonist Perfusion 0,1 µg/Kg/min < 5 min 30 min Most emergencies Nitroprusside Arterial and venous Perfusion 0,25-0,5 µg/Kg/min; Instant < 2 min Acute pulmonary edema. vasodilator Max. dose 8-10 µg/Kg/min (Max. 10 min) Nitroglycerin Venodilator Perfusion 5-100 µg/min 2-5 min 5-10 min ACS. Nicardipino Dihydropyridine Perfusion 5 mg/h 5-10 min 4-6 h Hyperadrenergic crisis. calcium antagonist Increase 2,5 mg/h cada 5 min (Max. 15 mg/h) Urapidilo Selective α-adrenergic Boluses 25-100 mg 3-5 min 4-6 h Perioperative antagonist at 5 min intervals hypertension. Phentolamine β-adrenergic blocker Boluses 1-5 mg 1-2 min 10-30 min Pheochromocytoma ACEI: angiotensin converting enzyme inhibitors; ACS: acute coronary syndrome.

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Enalapril curs within 1-2 minutes, lasting 3-10 minutes. The This is an ACE inhibitor that is available for recommended dose is 500-100 µg/min, depend- parenteral administration. It is used in doses of 1 ing on the desired effect (Table 4). mg and its effect starts after 15 minutes, lasting 12 to 24 hours. It has few side effects and only Nicardipine causes very slight symptomatic hypotension. It is This is a dihydropyridine-derivative calcium an- not recommended in cases of eclampsia or tagonist, with high cardiovascular selectivity and preeclampsia (Table 4). great cerebral and coronary vasodilatory activity. Onset of action is 5-10 minutes, and it has Fenoldopam been shown to reduce cerebral and cardiac is- This is an antihypertensive drug for parenteral chemia. Initial infusion of 5 mg/h, which can be administration. It is a dopamine agonist with po- stepped up by 2.5 mg/h every 5 minutes to a tent vasodilator action, especially renal. It causes maximum of 15 mg/h, or until the target BP is vasodilation which acts at the level of peripheral achieved19. dopamine receptors. Its effect starts at 5 minutes It is a good choice of drug in patients with and maximum response is reached at 15 minutes; ACS and congestive heart failure because in addi- action lasts between 30 and 60 minutes, and it tion to being a coronary artery vasodilator, it in- has no rebound effect20-22. Studies comparing creases stroke volume, thus favoring the correct fenoldopam with nitroprusside have demonstrated myocardial oxygen balance. It is also indicated in similar effectiveness but with fewer side effects23. hyperadrenergic crisis, and considered a good The recommended starting dose is 0.1 choice in eclampsia/preeclampsia. Its main draw- µg/kg/min. It improves creatinine clearance and back is its long half-life (4-6 h) (Table 4). sodium excretion in patients with severe hypertension with or without impaired renal function24-26. Urapidilo Its main contraindications are patients with glau- This is a new selective α-blocker. It produces coma (Table 4). reactive vasodilation without tachycardia, and acts centrally. It is used intravenously at doses of 25 Nitroprusside mg, and may be stepped up to 100 mg at inter- This is an arterial and venous vasodilator that vals of five minutes. It is not often used, but stud- decreases both preload and afterload27,28. It de- ies support its use in the treatment of prehospital creases cerebral blood flow and increases intracra- hypertensive emergencies and in perioperative hy- nial pressure so it is not recommended in cases of pertension36 (Table 4). hypertensive emergency with the brain as the target organ29-32 or in patients with ACS because it Phentolamine causes coronary steal33. It is a very powerful agent, This is an α-adrenergic blocker used in hyper- with very fast onset of action within seconds, and tensive crises induced by catecholamines a duration of 1-2 minutes with a half-life of 3-4 (Pheochromocytoma). Its effect is immediate, and minutes. It should only be used in patients with may cause angina and tachyarrhythmia (Table 4). normal liver and right kidney function, due to the risk of thiocyanite accumulation (Table 4). The duration of treatment should be as short as possible Specific situations and perfusion dose should not exceed 2 µg/kg/min (Table 4). Hypertension and aortic dissection

Nitroglycerine This constitutes a differential diagnosis to be This is a very potent venous vasodilator, and considered in every patient consulting the ED only affects arterial bed tone at high doses34. It with persistent chest pain accompanied by BP ele- causes hypotension and reflex tachycardia, exacer- vation. Three-quarters of patients with aortic dis- bated with volume depletion which is characteris- section that is not diagnosed and not treated tic of hypertensive emergencies. Nitroglycerin re- properly die within two weeks of the acute duces BP and reduces preload and cardiac output, episode; otherwise, survival at 5 years is 75%37. so it can have deleterious effects in patients with The recommendations in terms of BP values to altered cerebral or renal perfusion. It is the drug be achieved in the treatment of hypertension and of choice to reduce the BP and ischemic symp- aortic dissection range from SBP <140 and 110 toms in patients with ACS35. Its onset of action oc- mmHg38,39.

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Table 5. Therapeutic considerations depending on the type of hypertensive emergency Affected organ Complications Therapeutic considerations Contraindicated Aorta Dissection Labetalol/Esmolol + Fenoldopam/Nitroprusside Brain Ischemic stroke Labetalol/Fenoldopam Nitroprusside Brain Intraparenchymal hemorrhage Labetalol/Fenoldopam Nitroprusside Brain Hypertensive encephalopathy ACEI and/or labetalol Nitroprusside Heart Acute coronary syndrome Nitroglycerin + labetalol/esmolol/ACEI Nitroprusside Heart Heart failure/pulmonary edema Nitroglycerin/nitroprusside + loop diuretic Labetalol Placenta Eclampsia/preeclampsia Magnesium sulfate + Labetalol/Nicardipine ACEI/Nitroprusside Kidney Acute renal failure/hematuria/proteinuria ACEI?/Boluses Labetalol/fenoldopam perfusion ACEI?/Nitroprusside ACEI: angiotensin converting enzyme inhibitor.

While it is true that there are few randomized bolytic therapy, blood pressure should be reduced controlled trials that can provide clear guidance below 185/110 mmHg, to 180/105 mmHg47. The on how to treat hypertension in cases of aortic drug of choice is labetalol, and fenoldopam is the dissection40, a recommendation that should be main alternative. Nitroprusside is not recommend- borne in mind is that one should not employ a ed due to its well-known side effect of reducing vasodilator alone, because it promotes reflex cerebral blood flow and increasing intracranial tachycardia, increases speed of aortic ejection, pressure29-32 (Table 5). and therefore propagation of the dissection, since the dissection depends not only on raised BP, but Hypertension and cerebral hemorrhage also the speed of ventricular ejection. The best option for these patients is the combination of a Intracerebral hemorrhage (ICH) frequently pro- beta blocker and a vasodilator41. As beta-blockers, duces reflex hypertension, but unlike ischemic labetalol and esmolol are used, and the vasodila- stroke, this increase in BP does not usually im- tor traditionally used is sodium nitroprusside, al- prove spontaneously during the days immediately though fenoldopam is less toxic and improves re- after the onset of sympyoms48. nal perfusion (Table 5). Unlike ICH secondary to rupture of an arteri- ovenous malformation or to an intracerebral Severe hypertension with ischemic stroke aneurysm, there is no clear evidence that increased BP causes more bleeding in patients with Most patients with acute ischemic stroke pres- spontaneous ICH, and a sharp decrease of BP may ent high BP on ED consultation, regardless of the compromise brain perfusion49. etiology or whether they are hypertensive or There are no specific recommendations on not42,43. High BP does not per se constitute a hy- what specific level of BP is most beneficial for a pertensive emergency, but is rather a physiologi- patient with ICH, although the following evidence cal mechanism designed to maintain perfusion is relevant: pressure in the area affected by cerebral ischemia. – Increased bleeding has been shown to be This increase in BP normalizes progressively and more common in patients with isolated systolic spontaneously. For this reason, these patients BP, but it is not known whether this increase is should be assessed with caution, because rapid BP due to increased ICH itself, leading to increased reduction may worsen the ischemic area. The intracranial pressure49. However, we do know that: common practice of "normalizing" BP in acute is- – Isolated systolic pressure 210 mmHg has chemic stroke patients is potentially dangerous, as not been clearly linked with increased bleeding or shown by some studies44. Hypertension in the neurological deterioration50. acute phase of stroke has not been shown to have – A 15% reduction in MAP does not affect a deleterious effect and some studies suggest a cerebral blood flow51. protective role45. Depending on the upper limit of – Reducing SBP to <160/90 mmHg during the BP self regulation by the brain, it is advisable not first 6 hours of onset of ICH is associated with to initiate antihypertensive treatment in these pa- better functional outcome52. tients unless TOD has been established or throm- It is important, likewise, to individualize BP bolytic treatment is being evaluated or SBP >220 treatment based on the patient's prior baseline, mmHg or DBP >120 mmHg46,47. In this context, it assess the cause of bleeding, age and the signs of is recommended not to allow more than a 15% intracranial hypertension53. The drug of choice in decrease of BP values in the first 24 hours. In the these cases is also labetalol, and the second op- event that the patient is a candidate for throm- tion is fenoldopam (Table 5).

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Hypertensive encephalopathy mental studies have shown that, in the early stages of ACS, excessive renin-angiotensin axis ac- This diagnosis is made by exclusion, after cere- tivation occurs, and some studies ascribe increas- bral hemorrhage and ischemic stroke have been ing importance to this finding56. The treatment reasonably ruled out. It is characterized by signs goal in a hypertensive emergency with ACS is, and symptoms such as severe headache, altered firstly, to reduce myocardial oxygen demand, and state of consciousness, seizures, and papilledema, secondly, to block neurohumoral action. For the without neurological deficit. The mechanism re- former, the use of intravenous nitroglycerin is in- sponsible has been attributed to a sudden indicated. Nitroprusside is contraindicated because crease in pressure of cerebral perfusion, secondary it may cause a decrease in transmural flow. Block- to a rapid, abrupt increase in BP, resulting in ede- ing the neurohumoral system may be achieved ma and reduced cerebral blood flow. This entity is with beta-blockers, such as labetalol (alpha and usually found in patients with untreated primary beta adrenergic receptor blocker) and esmolol hypertension and a rapid, abrupt increase of BP, (cardioselective beta blocker), or intravenous but also in patients with other predisposing con- enalapril. ditions, such as renovascular hypertension, ACS arising from cocaine use is characterized glomerulonephritis, pheochromocytoma and by adrenergic receptor stimulation, so the treat- eclampsia. It has been known for years that the ment of choice is alpha-adrenergic blockers. Beta- cause of this rise in BP is due, in most cases, to blockers are formally contraindicated since they overproduction of renin and angiotensin II in re- may give rise to a alpha-adrenergic storm and en- sponse to renal ischemia, although other mecha- hance the toxicity of cocaine (Table 5). nisms have been identified, such as sympathetic vasoconstriction, blood-brain barrier disruption Crisis mediated by excessive secretion or release due to alterations in cerebral blood flow and over- of catecholamines production of angiotensin II, which promotes oxidative stress in brain vessels54. This is the case of hypertensive crisis related The etiologic role of overstimulation of the with the consumption of recreational drugs of renin-angiotensin system underlies focus of treat- abuse such as cocaine, amphetamines, LSD or Ec- ment, so drugs that block this axis are used. The stasy, and more rarely in the context of pheochro- drugs of choice are oral or intravenous ACE in- mocytoma, consumption of monoamine oxidase hibitors, such as captopril and enalapril, respec- or abrupt cessation of treatment with beta-adren- tively. Likewise, an ACE inhibitor with a beta- ergic agonists. adrenergic blocker, such as labetalol, interrupt the Patients with pheochromocytoma present renin angiotensin axis at various points and help headache, alternating periods of elevated BP, to maintain cerebral blood flow while decreasing tachycardia and flushing that follow periods of systemic BP. Diuretics and vasodilators are not ad- normotension, while subjects that have taken visable for this reason (Table 5). recreational drugs show tachycardia, diaphoresis, hypertension and changes in mood and level of Hypertensive left ventricular failure consciousness. The treatment drug of choice is phentolamine, to which calcium channel blockers This is characterized by the presence of signs can be added. and symptoms of intravascular volume overload In clinical situations characterized by sympa- and interstitial or secondary manifestations of tis- thetic overstimulation, beta-adrenergic antago- sue hypoperfusion, such as dyspnea. Elevated BP nists should be avoided to prevent beta-receptor in these cases can be both the cause and the re- antagonism, which would result in response acti- sult of acute pulmonary edema. The treatment of vation of alpha adrenergic activity, with a sec- choice is based on the use of vasodilators such as ondary effect of increasing BP level. Although la- nitroglycerin or nitroprusside with an intravenous betalol has a beta and alfha blocking effect, it is loop diuretic55. Drugs that decrease contractility, not recommended for use in these cases. The such as beta-blockers, should be avoided (Table 5). drugs that should be used in this circumstance include nitroglycerin, nicardipine or verapamil in Hypertension with acute coronary syndrome combination with intravenous benzodiazepine57. Also, fenoldopam, nitroprusside, nitroglycerin Like acute pulmonary edema, ACS can develop and phentolamine can be used as alternatives58 in the context of a peak in hypertension. Experi- (Table 5).

216 Emergencias 2010; 22: 209-219 HYPERTENSION, HYPERTENSIVE CRISIS, AND HYPERTENSIVE EMERGENCY: APPROACHES TO EMERGENCY DEPARTMENT CARE

Accelerated-malignant hypertension pre-eclampsia includes volume expansion, magne-

sium sulfate (MgSO4) for seizure prophylaxis and The picture of severe hypertension associated BP control62. Magnesium sulphate is administered with edema of the papilla (Hypertensive retinopa- with a loading dose of 4-6 g in 5% dextrose solu- thy grade-IV Keith-Wagener) is called accelerated- tion during 15-20 minutes followed by a continu- malignant hypertension. If retinopathy is of grade- ous infusion of 1-2 g/h. The objective, in addition III (bleeding and exudates) it is called accelerated to treating severe hypertension, is not to compro- hypertension. In this case, as in hypertensive en- mise cerebral and placental blood flow, since in cephalopathy, the rapid increase in BP is mostly this situation BP is most labile. The drug of choice caused by overproduction of renin and an- for these patients is labetalol since it is safe and ef- giotensin II in response to renal ischemia59. This fective, easily titrated and has a short half-life63. situation very rarely presents as de novo hyperten- Nicardipine is a good alternative, while nitroprus- sion, and generally presents in the context of side and ACE inhibitors are formally contraindicat- long-standing hypertension or, more often, hyper- ed in pregnancy. Classically hydralazine used to be tension secondary to renovascular hypertension, recommended, but it is associated with side effects scleroderma, or vasculitis. Its incidence before the such as headache, nausea and vomiting, which advent of antihypertensive drugs was 7%, where- mimic the picture, so in these situations it is not as currently this is 1% of hypertensive patients, recommended as a first-line option64 (Table 5). characteristically those of a relatively young age60. Unless treated with antihypertensive drugs, medi- um-term mortality is high, associated with long- References term cardiac and renal sequelae in most patients. 1 Gifford R. Management of hypertensive crises. JAMA. 1991;266:829-35. In these patients the objective is to reduce BP 2 Mancia G, De Backer G, Dominiczak A. Management of Arterial by less than 25% of initial BP or to achieve a DBP Hypertension of the European Society of Hypertension; European So- ciety of Cardiology. Guidelines for the Management of Arterial of 100-105 mmHg61. Hypertension: The Task Force for the Management of Arterial Hyper- The etiologic role of overstimulation of the tension of the European Society of Hypertension (ESH) and of the Eu- ropean Society of Cardiology (ESC). J Hypertens. 2007;25:1105-87. renin-angiotensin axis conditions treatment and 3 JNC VII-The Seventh Report of the Joint National Committee on Pre- the use of drugs that block this axis, and although vention, Detection, Evaluation, and Treatment of High Blood Pressu- re. JAMA. 2003;289:2560-72. the use of ACE inhibitors is recommended by 4 Lip G, Beevers G. The failure of malignant hypertension to decline: a some authors, others claim otherwise61. Captopril survey of 24 years experience in a multiracial population in England. J Hypertens. 1994;12:1297-305. has an onset of action between 30-60 minutes. 5 Graves, JW. Prevalence of blood pressure cuff sizes in a referral prac- Intravenous enalapril has a rapid effect and there- tice of 430 consecutive adult hypertensives. Blood Press Monit. 2001;6:17-20. fore should be avoided (Table 5). Boluses of la- 6 Decker WW, Godwin SA, Hess EP, Lenamond CC, Jagoda AC. Clinical betalol are recommended, and continuous infu- Policy: Critical Issues in the evaluation and Management of Adult Pa- tients with asymptomatic Hypertension in the Emergency Depart- sion of enoldopam is a very good alternative, ment. Ann Emerg Med. 2006;47:237-49. since for cases of hypotension its half-life is 30 7 Chernow SM, Iserson KV, Criss E. Use of the emergency department for hypertension screening: a prospective study. Ann Emerg Med. minutes. 1987;16:180-2. 8 Varon J, Marik P. Hypertensive crises. Challenges and management. Chest. 2000;118:214-27. Preeclampsia and eclampsia 9 Strandgaard S, Olesen J, Skinhoj E. Autoregulation of brain circulation in severe arterial hypertension. BMJ. 1973;1:507-10. 10 Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis Hypertension is one of the processes that can and management: Part II: therapeutic management and follow-up. complicate a pregnancy. This syndrome, charac- Circulation. 2003;108:772-8. 11 Estrera AL, Miller CC, Safi, HJ, Goodrick JS, Keyhani A, Pozat EE, et al. terized by BP >140/90 mm Hg and proteinuria Outcomes of medical management of acute type B aortic dissection. >300 mg/24 h, usually occurs after 20 weeks of Circulation. 2006;114:1384-9. 12 Laguna del Estal P. Crisis hipertensivas. Emergencias. 1999;11:339-42. gestation62. Depending on the series of patients, it 13 Gales MA. Oral antihypertensives for hypertensive urgencies. Ann may affect up to 12% of pregnancies, and is esti- Pharmacoth. 1994;28:352-8. 14 Kanot, J, Allonen, H, Kleimola T. Pharmacokinetics of labetalol in he- mated to be involved in 18% of maternal deaths, althy volunteers. Int J Clin Pharmacol Ther Toxicol. 1981;19:41-4. so pregnancy-induced hypertension can be life- 15 Pearce CJ, Wallin JD. Labetalol and other agents that block both α- and β-adrenergic receptors. Cleve Clin J Med. 1994;61:59-69. threatening63. 16 Wallin JD. Adrenoreceptors and renal function. J Clin Hyperten. Accompanied by headache, visual distur- 1985;1:171-8. 17 Marx PG, Reid DS. Labetalol infusion in acute myocardial infarction bances, increased serum creatinine, thrombocy- with systemic hypertension. Br J Clin Pharmacol. 1979;8:233S-238S. topenia, hemolytic microangiopathic anemia, in- 18 Olsen KS, Svendsen LB, Larsen FS, Paulson OB. Effect of labetalol on cerebral blood flow, oxygen metabolism and autoregulation in he- creased dehydrogenase lactate and liver enzymes. althy humans. Br J Anaesth. 1995;75:51-4. Delivery is the definitive treatment for 19 Varon J, Marik PE. Clinical Review: The management of hypertensive crises. Critical Care. 2003;7:374-84. preeclampsia and eclampsia. Initial treatment of 20 Bodmann KF, Troster S, Clemens R, Schuster HP. Hemodynamic pro-

Emergencias 2010; 22: 209-219 217 E. Gómez Angelats et al.

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218 Emergencias 2010; 22: 209-219 HYPERTENSION, HYPERTENSIVE CRISIS, AND HYPERTENSIVE EMERGENCY: APPROACHES TO EMERGENCY DEPARTMENT CARE

Hipertensión arterial, crisis hipertensiva y emergencia hipertensiva: actitud en urgencias

Gómez Angelats E, Bragulat Baur E La elevación de las cifras de presión arterial (PA) constituye un motivo de consulta frecuente en los servicios de urgencias. Es importante tener en cuenta que esta elevación por si sola no define si se trata de una urgencia o de una emergencia, sino el cuadro que acompaña a dicha elevación, por lo que es primordial diferenciar, de entrada, ambas situa- ciones. La emergencia hipertensiva se caracteriza por la existencia de una lesión aguda evidente de órgano diana, y que se presenta en forma de la encefalopatía hipertensiva, hemorragia intracraneal, síndrome coronario agudo, insufi- ciencia cardiaca con edema agudo de pulmón, disección de aorta, eclampsia-preeclampsia o hipertensión acelerada. Requiere una reducción inmediata aunque no brusca de las cifras de PA por vía parenteral. En contraposición, la urgencia hipertensiva es aquel cuadro caracterizado por un aumento severo de las cifras de PA sin evidencia de lesión aguda o progresiva de órgano diana y que require una reducción progresiva de dichas cifras en el plazo de 24 horas a varios días con fármacos administrados por vía oral. Existe un gran número de fármacos para el manejo de esta patolo- gía, y no se ha demostrado de forma fehaciente que un fármaco, ya sea parenteral o no, sea mejor que otro para re- ducir las cifras de PA. Sin embargo, en función del cuadro acompañante y de las características individuales de cada paciente, se pueden hacer recomendaciones particulares, como se muestra en la presente revisión. [Emergencias 2010;22:209-219]

Palabras clave: Hipertensión arterial. Crisis hipertensiva. Emergencia hipertensiva.

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