2. What it is important  Malignant HTN was used to compare the prognosis of this patients with cancer  Improvement of its outcome with advance treatment  1-year mortality :  1928 %80  1955 %50  1989 %10  5 year survival 70 – 90 %

3. Hypertensive crisis  Management of hypertensive crisis in the ED will continue to challenge clinicians because of the lack of randomized clinical trials. Expert opinion and clinical judgment will continue to guide the management of hypertension Expert opinion and clinical judgment will continue to guide the management of hypertension

5. New terminology  Term of malignant and accelerated HTN replaced with : Hypertensive emergency Hypertensive emergency Hypertensive urgency Hypertensive urgency

6. Definition : Most defined as a sudden increase in systolic and diastolic BP > 180/120 mmhg Urgency Marked HTN not associated with TOD Emergency Marked HTN associated with Target Organ Damage/ Dysfunction (TOD )

7. Hypertensive Emergencies  Hypertensive Encephalopathy  Cerebral hemorrhage  Disecting aortic aneurym  Acute Left ventricular failure with pulmonary edema  Acute myocardial ischemia  Eclampcia  Acute renal failure  Symptomatic microangiopathic hemolytic anemia

8. Emergency HTN ( Special )  Postoperative HTN defined as a SBP > 190 mmHg and/or DBP > 100 mmHg on two consecutive readings following 2 hour of surgery  Postoperative hypertension may have significant adverse sequelae in both cardiac and non-cardiac patients  The presence of a SBP> 169 mmHg or a DBP> 109 in a pregnant woman considered as emergency HTN that requires immediate pharmacologic T.

9. Epidemiology  1% of patients with HTN will develop a crise during lives  Before the advent of therapy, in up to 7%  As essential HTN much higher among African-Americans and the elderly and men  In a study with > 14000 emergency department visit : 5 out of 1,000 patients admition to the EDs urgency HTN accounted %76 emergency %24 of HTN related visit

10. major risk factors for HTN emergencies  Medication non adherence  Poorly controlled chronic hypertension  Substance abuse  Poor access to primary care

11. Etiology  Can develop :  De novo  De novo  Can complicate : Underlying essential Underlying essential Secondary hypertension Secondary hypertension

12. Etiology of HTN crisis  Essential hypertension :  In white accounts 20–30% of HTN crisis.  In blacks accounting 80% of crisis.  Secondary HTN  Renal parenchymal disease accounts for up to 80% of all secondary causes: with chronic pyelonephritis and glomerulonephritis being the most common with chronic pyelonephritis and glomerulonephritis being the most common

13. Secondary cause of HTN Crisis Cause Example Renal parenchylmalChronic pyelonephritis Primary glomerulonephritis Tubulointerstitia nephritis Systemic disease with renal involvement SLE Systemic sclerosis Vascolitis Renovascular disease Atherosclerotic disease Fibromuscular displasia Polyarteritis nodosa Endocrine Pheochromocytoma Primary hyperaldosteronism Cosing syndrome

14. pathogenesis MechanismsExample RAS dependentAcute glomerulonephritis Scleroderma renal crisis Unilateral renal artery stenosis Excess catecholamine releasePheochromocytoma Monoamine oxidase inhibitor crisis Cocaine intoxication Spinal cord injery Volume overloadRenal failure Bilateral renal artery stenosis

15. Pathogenesis  The most clinical setting for a HTN urgency is the Chronic, often untreated, poorly controled hypertensives whose usual BP > 180/110  In many of these patients chronically elevated BP dose not affect on target organ perfusion Because of autoregulation

16. Autoregulation  Is the ability of blood vessels to dilate or to constrict in response to changes in perfusion pressure and thereby to maitain normal organ perfusion  Present in brain and kidney and cronary arteries  Involve L-type calcium channels  In normotensive can maintain flow over a wide range of MAP ( 80 – 150 mmhg )

17. Impaired autoregulation  Rising of BP > autoregulatory range  Progressive disease of arterioles in both cerebral and renal circulations  when autoregulation pharmacologically inhibited ( dihydropyridines and furosemide )

18. Renal autoregulation 80 120 160 Systemic pressure Impaired autoregulation Normal autoregulation Intraglomerular pressure

22. Target organ damage Primary insult Inability of outoregulatory mechanisms to maintain normal perfusion pressure in brain and kidney Increased vascular wall permeability Cell proliferation Platlet and coagulation cascade activation Further vascular damage and tissue ischemia Coupled with Release of vasoactive substances ( RAS,catecholamines, endothelin,vasopressin ) A vicious circle between elevated BP and vascular injury The mechanical shear forces endothelial dysfunction expression of inflammatory markers such as endothelin-1, endothelial adhesion molecules, and cytokines

23. A vicious circle  High BP Vascular damage ischemia Vasoactive substances

24. Structural changes ?  Fibrinoid necrosis of small arteriese and arterioles in brain and kidney  Cerebral edema

25. Clinical presentation

26. Diagnostic evaluation HistoryPMH of HTN,treatment, symptoms,cardiac, cerebral and visual change, intake of pressor agent, sympathomimetics, illicit substances Physical examRepeat BP measurements ( both hand and Leg Cardiac, Vascular, Pulmonary Neurolog ic, Optic fundi Laboratory studiesFull blood count, urinanalysis, Cr, Urea, electrolytes, and if Secondary Suspected : Plasma Renin activity, aldosterone, catecholamines Electrocardiography CXRay According to clinical presentationBrain CT or MRI, Echocardiography, Thoracoabdominal CT or MRI, abdominal Sono

27. Treatment of emergency HTN.General view  Parentral agents may be initiated in emergency department  Should be admited in ICU for : Continous BP monitoring Continous BP monitoring Clinical surveillance Clinical surveillance Continoued parentral adminstration Continoued parentral adminstration  Specific BP level do not determine the severity and emergency situation because autoregulatory changes may vary between individuals  Sudden lowering of BP in to a normal could lead to inadequate tissue perfusion

28. Treatment of emergency HTN.General view  Mean BP should be reduced up to 20 – 25% within the first few min to an hour  Dias BP between 100 – 110 mmhg or reduction of 25% compared with baseline is appropriate in the next 2-6 hours  Reduction of dias BP to less than 90 or by 35% of initial mean BP may be induce major organ dysfunction, coma, and death

29. Treatment of emergency HTN.General view  If the level of BP reduction well tolerated, gratual reduction to ward below 140/90 the next 24 -48 hour  Once BP is stabilized with parenteral therapy, the transition to oral therapy can begin within 6 to 12 hours.  Oral long acting Ca channel blocker with either a α and β blocker as carvedilol or nebivolol or RAS blocker and tapering of intravenouce medication during 1 – 2 hour  Assessment of patient volume status is important because pressure natriuresis may induce hypovolumia thus resucitation may improve tissue perfusion

30. Treatment of emergency HTN General view ( exceptions )  In patients with acute strock there is no evidence to support BP lowering  Patients with aortic dissection, systolic Bp lowered to< 100  Patients how needed thrombolytic therapy

34. Treatment of emergency HTN Specific ( Nitroprusside ) AdvantagesDidadvantages Easily titrated Inexpensive Effectiveness in all types Need to invasive monitoring Toxic metabolite as thiocyanate and cyanide that contraindicated in pregnancy and limited use in renal and hepatic dysfunction Increase ICP Obliterate cerebral autoregulation Reduce regional coronary blood flow Because toxicity issues some authors suggest that nitroprusside be used only when alternative drug choices are not available

35. Nitroglycerin  Is a venodilator  Acts as an arteriolar dilator only in high doses  Similar to nitroprusside, it can compromise cerebral perfusion and hence is not used in hypertensive encephalopathy  It is choice in HTN emergencies associated : acute pulmonary edema acute pulmonary edema acute coronary syndromes acute coronary syndromes

36. Treatment of emergency HTN Specific ( nicardipine )  A dihydropyridine CCB  with intermediate onset and duration of effect  Prolonged half life  Strong cerebral and coronary vasodilator  Useful in most emergency HTN especially in patients with IHD

37. Treatment of emergency HTN Specific ( fenoldopam )  Selective agonist of dopaminergic 1 receptors located mainly in the renal arteries with lessr density in the coronary and cerebral arteries  Comparable with nitroprusside in BP lowering with  Benefical renal effects ( increse diuresis, natiuresis and Cr clearance  Has very short half life  Mostly useful for BP lowering in renal impairement, heart failure, vascular surgery  Caution, in glaocoma as it increase intra occular pressure  Expensive Begin at 0.1 μ g /kg/min and increase 0.1 – 0.2 μ g/kg/min

38. Treatment of emergency HTN Specific ( Labetalol )  Non selective α 1 and β blocker 1/7  Rapid onset of action  Potent and sustained effect  Low toxicity  Reduce peripheral vascular resistant  Indicated in aortic dissection, acute coronary syndrome, hypertensive encephalopathy,and adernergic crisis  Contraindicated in heart failure, heart block, COPD

39. Treatment of emergency HTN Specific ( clevidipine )  Third generation of dihydropyridine CCB  Short acting selective arteriolar vasodilator  Its metabolism is not affected by renal or hepatic function  Safe in post operative HTN

40. Treatment of hypertensive emergency  Withdrawal of antihypertensive therapy :  Abrupt discontinuation of a short-acting sympathetic blocker (such as clonidine or propranolol ) can lead to severe hypertension and coronary ischemia due to upregulation of sympathetic receptors.  Control of the BP can be achieved by readministration of the discontinued drug and, if necessary, phentolamine, nitroprusside, or labetalol

41. Treatment of hypertensive emergency  Acute increase in sympathetic activity :  Drug withdrawal  Pheochromocytoma  Autonomic dysfunction, as in the Guillain-Barré syndrome or post-spinal cord injury  The use of sympathomimetic drugs, such as phenylpropanolamine, cocaine, amphetamines, phencyclidine  Combination of an MAO inhibitor and the ingestion of tyramine-containing foods (such as most fermented cheeses, smoked or aged meats, Chianti, champagne, and avocados)  Phentolamjne or nitroprusside  Phentolamjne or nitroprusside  Administration of a beta blocker alone is contraindicated, since inhibition of beta-receptor-induced vasodilation results in unopposed alpha-adrenergic vasoconstriction and a further rise in BP

42. Treatment of hypertensive emergency  Pregnancy :  Intravenous labetalol and hydralazine

43. Treatment of urgency HTN  BP lowering should occur during a longer time within 2-4 hour to level 160/100  Adequate follow up  Almost all antihypertensive drugs lower BP effectively  Captopiril, clonidine, labetalol ……..  Short acting nifedipine is now contraindicated by higher incidence of stroke, MI, and death  Oral clonidin 0.1 – 0.2 mg commonly used but patients should not be routinely discharged  Furosemide can lower BP if HTN related to volume ( is uncommon )  Long acting CCB ie nifedipine XL, amlodipine and isradipine have key role, but due to inhibition of renal autoregulation should not use as initial treatment.

45. Treatment of hypertensive emergency  Hypertensive encephalopathy :  Reduction of the BP < 25 percent of the initial value within the first 24 hours  with a parenteral vasodilator  Nitroprusside  Nicardipine  Clevidipine labetalol  labetalol  Phenoldopam

46. Treatment of hypertensive emergency  Ischemic stroke or subarachnoid or intracerebral hemorrhage :  The benefit of reducing the BP in these disorders must be weighed against possible worsening of cerebral ischemia induced by the thrombotic lesion or by cerebral vasospasm

47. Treatment of hypertensive emergency  Acute pulmonary edema :  Acute left ventricular failure due to systolic dysfunction should be principally treated: Nitroprusside Nitroprusside or nitroglycerin Nitroprusside or nitroglycerin with a loop diuretic is the regimen of choicenitroglycerinNitroprusside nitroglycerin hydralazine labetalol hydralazine labetalol Drugs that increase cardiac work ( hydralazine ) or decrease cardiac contractility ( labetalol or other beta blocker) should be avoidedhydralazine labetalol

48. Treatment of hypertensive emergency  Angina pectoris or acute myocardial infarction :  Beta adrenergic blockers should be administered to all patients without contraindications who experience a myocardial infarction. n itroprussiden itroprussideand nitroglycerin  Intravenous parenteral vasodilators, principally n itroprussideand nitroglycerin, are effectivenitroglycerinn itroprussidenitroglycerin hydralazine  Drugs that increase cardiac work ( hydralazine ) are contraindicated. hydralazine

49. Treatment of hypertensive emergency  Aortic dissection :  An intravenous beta blocker should be given to reduce the heart rate below 60 beats/min and maintain the sys BP between 100 to 120 mmHg or the lowest level  Nitroprusside can be added to further control blood pressure but should not be given without first controlling the heart rate with beta blockade.

51. Definitions  Different terms have been applied to acute severe elevations in blood pressure  That may be somewhat confusing

52. Although not specifically addressed in the JNC-7 report patients with a SYS BP > 179 or Dias BP > 109 mmHg are usually defined as having 'severe or accelerated' hypertension

53. Pathophysiology  The factors that lead to the severe and rapid elevation of blood pressure in patients with malignant hypertension are poorly understood. The rapidity of onset suggests a triggering factor superimposed on pre-existing hypertension. The risks for developing malignant hypertension are related to the severity of the underlying hypertension, and therefore the role of mechanical stress on the vessel wall appears to be critical in its pathogenesis. The release of humoral vasoconstrictor substances from the stressed vessel wall is thought to be responsible for the initiation and perpetuation of the hypertensive crisis

54.  ]. Increased blood pressure results in endothelial damage, with local intravascular activation of the clotting cascade, fibrinoid necrosis of small blood vessels, and release of vasoconstrictor substances [40,41]. This leads to a vicious cycle of further vascular injury, tissue ischemia, and release of vasoconstrictor substances [40,41]. The volume depletion that results from pressure natriuresis further simulates the release of vasoconstrictor substances from the kidney. The release of vasoconstrictor substances from the kidney has long been postulated to play a central role in the pathophysiology of malignant hypertension [42]. Activation of the renin–angiotensin system has been strongly implicated in the initiation and perpetuation of the vascular injury associated with malignant hypertension4041404142

55.  ]. In addition to activation of the renin–angiotensin system vasopressin, endothelin and catecholamines are postulated to play important roles in the pathophysiology of hypertensive emergencies [46- 49].46 49

56.  Mater Sociomed. 2014 Feb; 26(1): 12-16

66. Emergency HTN Or HTN Crises

69. Hydralazine 10 – 20 mg IV, 10 – 20 min, 30 min, tachycardia flushing, headache, vomiting, eclapsia110-20 mg IV0-20 mg IV