1. HYPERTENSIVE EMERGENCIES Mostafa alshamiri

2. Discussion Categories Epidemiology Etiology/pathophysiolog Managment Treatment Prognosis Take home massage

3. Case Scenarios A 56 yo CM with no significant PMH presents to the ER with headache,found to have BP 210/110mmHg and papilledema. An 82 yo male with h/o HTN,chronic renal insufficiency presents for a routine physical,found to have BP of 230/130mmHg. A 76 yo female is brought to the ER by the family due to altered mental status.BP is 240/110 mmHg with no focal neuro findings.

4. Definition Sustained abnormal elevation of blood pressure

5. HYPERTENSION(JNC-7class.) SBP-mmHgDBP-mmHg NORMAL <120 <80 PREHYPERTENSION 120-139 or 80-89 STAGE 1 140-159 or 90-99 STAGE 2 >=160 >=100

6. Comparative Prevalence of hypertension and the expected hypertension population in each country Journal of Hypertension 2005, Vol 23 No 6

7. Benefits of Lowering BP Average Percent Reduction Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure50%

8. Key Point For every 20 mm Hg increase in SBP or 10 mm Hg increase in DBP – the risk of death from stroke, IHD, or vascular disease DOUBLES! For every 20 mm Hg decrease in SBP or 10 mm Hg decrease in DBP – the risk of death from stroke, IHD, or vascular disease IS CUT IN HALF!

9. HYPERTENSIVE EMERGENCY/URGENCY

10. Hypertensive Emergencies/crises Patients with marked BP elevations (> 180/120 mm Hg) and acute TOD (e.g., encephalopathy, myocardial infarction, unstable angina, pulmonary edema, eclampsia, head trauma, life-threatening arterial bleeding, or aortic dissection) require hospitalization and parenteral drug therapy. Hypertensive Urgencies  Patients with markedly elevated BP but without acute TOD usually do not require hospitalization, but should receive immediate combination oral antihypertensive therapy.  Although not specifically addressed in the JNC 7 Report, patients with a systolic blood pressure greater than 179 mmHg or a diastolic blood pressure that is greater than 109 mmHg are usually defined as having 'severe or accelerated' hypertension

11. Historical background of HTN emergency The term 'malignant hypertension' has been used to describe a syndrome characterized by elevated blood pressure accompanied by encephalopathy or acute nephropathy. However, this term has been removed from national and international blood pressure control guidelines

12. Other entity- emergency Postoperative hypertension has arbitrarily been defined as a systolic blood pressure greater than 190 mmHg and/or diastolic blood pressure greater than 100 mmHg on two consecutive readings following surgery The presence of a systolic pressure greater than 169 mmHg or a diastolic pressure greater than 109 mmHg in a pregnant woman is considered a hypertensive emergency that requires immediate pharmacologic management

13. ETIOLOGY Essential hypertension : Inadequate blood pressure control and noncompliance are common precipitants Renovascular Eclampsia/pre-eclampsia Acute glomerulonephritis Pheochromocytoma Anti-hypertensive withdrawal syndromes Head injuries and CNS trauma Renin-secreting tumors Drug-induced hypertension Burns Vasculitis TTP Idiopathic hypertension Post-op hypertension Coarctation of aorta

14. Epidemiology of hypertensive crisis. Hypertension is an extremely common clinical problem, affecting approximately 50 million people in the USA and approximately 1 billion individuals worldwide. Approximately 1% of these patients will develop acute elevations in blood pressure at some point in their lifetime 20-30% in patient with emer/urg secondary to uncontrolled essential HTN while in black it is 80%.

15. BLOOD FLOW BP = PVR X CO (HR X SV) MAP = DBP + 1/3 PP (SBP-DBP) CPP = MAP – ICP (normal, ICP =10) Cpp between 70-90, some consider 50-150 Increase MAP will increase CPP and vasa versa. CBF maintained near-constant by auto regulatory mechanism (vaso- conestrection/dilation ), despite variation in CPP, however, has upper and lower limit beyond which CBF can no longer be controlled. When MAP increases >>> increases CPP >>> and hyperperfusion >> brain edema & progressive brain dysfunction & ischemia. Decreased CBF >> brain hypoxia and hypo-perfusion symptoms ( headache, nausea, dizziness,altered sensorium, lethargy & ultimately infarction). Normal BP maintain auto regulation of MAP between 50 to 150 Overzealous BP reduction can lead to permanent neurological damage.

16. Auto-regulation curve

18. PATHOPHYSIOLOGY NORMAL AUTOREGULATION RISE IN BP ARTERIAL AND ARTERIOLAR CONSTRICTION Normal flow.(flow=P/r) RISE IN BP FAILURE OF VASOCONSTRICTION ENDOTHELIAL DAMAGE (due to shear stress on the wall) AUTOREGULATION FAILURE

19. PATHOPHYSIOLOGY BP=PVR*CO(SV*HR) Rate at which MAP rises more important than absolute rise. Acute rise in BP Failure of vasoconstriction Endothelial by autoregulation damage FIBRINOID Activates coagn and Depsn. of proteins/ NECROSIS inflammation fibrinogen in vessel wall  RAAS plays an important role in initiating and perpetuating BP rise by causing vasoconstriction and fluid retention.

20. CARDIOVASCULAR SYSTEM The cardiovascular system is affected as increased cardiac workload leads to cardiac failure; this is accompanied by pulmonary edema, myocardial ischemia, or myocardial infarction.

21. RENAL SYSTEM The renal system is impaired when high BP leads to arteriosclerosis, fibrinoid necrosis, and an overall impairment of renal protective autoregulation mechanisms. This may manifest as worsening renal function, hematuria, red blood cell (RBC) cast formation, and/or proteinuria.

22. CENTRAL NERVOUS SYSTEM The CNS is affected as the elevated BP overwhelms the normal cerebral autoregulation. Under normal circumstances, with an increase in BP, cerebral arterioles vasoconstrict and cerebral blood flow (CBF) remains constant. During a hypertensive emergency, the elevated BP overwhelms arteriolar control over vasoconstriction and autoregulation of CBF. This results in transudate leak across capillaries and continued arteriolar damage. Subsequent fibrinoid necrosis causes normal autoregulatory mechanisms to fail, leading to clinically apparent papilledema, the sine qua non of malignant hypertension. The end result of loss of autoregulation is hypertensive encephalopathy.

23. Hypertensive encephalopathy Hypertensive encephalopathy is an acute organic brain syndrome or delirium related to cerebral edema Result from loss of cerebral vascular auto regulatory function in the setting of severely elevated blood pressure. Characterized initially by Headache Nausea, and vomiting, followed by Altered mental status and/or seizure if hypertension is not treated. Hypertensive encephalopathy is a diagnosis of exclusion; other causes must be ruled out

24. Management of hypertensive emergency HISTORY PHYSICAL EX LABARATORY DRUGS THERAPY

25. The ideal pharmacologic agent for the management of hypertensive crises would be : Fast-acting, Rapidly reversible Titratable Without significant side effects

27. Treatment-1 Initial considerations : Place patient who is not in distress in a quiet room and reevaluate after an initial interview. In one study, 27% of patients with an initial DBP >130 mm Hg had their DBP fall below critical levels after relaxation without specific treatment. Consider the context of the elevated BP (eg, severe pain) Screen for end-organ damage- Patients with end-organ damage usually require admission and rapid lowering of BP using iv meds.Suggested meds depend on the end-organ system damaged. Patients without evidence of end-organ effects may be discharged with follow–up. It is a misconception that a patient should not be discharged from the ER with elevated BP.Giving oral meds such as nifedipine to rapidly lower BP may be dangerous as the BP may have been elevated for sometime and there may be organ hypoperfusion.Acute control has not improved long term mortality and morbidity rates.

28. TREATMENT-2 DRUGS THERAPY HTN-URGENCY The initial goal is to reduce blood pressure to 160/110 mm Hg over several hours to days using conventional oral therapy. Mean arterial pressure should be reduced by no more than 25% within the first 24 hours HTN-EMERGENCY The ideal rate of blood pressure lowering is unclear, but reducing the mean arterial pressure by 10% during the first hour and an additional 15% within the next 2 to 3 hours has been recommended

29. The majority of patients with severe hypertension (diastolic pressure > 109 mmHg) will have no acute end-organ damage (hypertensive urgencies). In these patients the blood pressure should be lowered gradually over a period of 24–48 hours, usually with oral medication. Rapid reduction in blood pressure in these patients may be associated with significant morbidity. In patients with true hypertensive emergencies, rapid but controlled lowering of blood pressure is indicated to limit and prevent further organ damage. However, the blood pressure should not be lowered to normal levels. TREATMENT - 3

30. TREATMENT - 4 Most patients with hypertensive emergencies are chronically hypertensive and will have a rightward shift of the pressure– flow (cerebral, renal, and coronary) autoregulation curve. Rapid reduction in blood pressure below the cerebral, renal, and/or coronary auto-regulatory range will result in a marked reduction in organ blood flow, leading to ischemia and infarction. For this reason all patients with a hypertensive emergency should be managed in an intensive care unit, where the patient can be closely monitored. Intra-arterial blood pressure monitoring may be required in patients with blood pressure that is labile and difficult to control.

31. Treatment-HTN emergency (crisi)-5 Reductions in diastolic blood pressure by 10–15% or to about 110 mmHg is generally recommended. This is best achieved by an continuous infusion of a short acting, titratable, parenteral antihypertensive agent. In patients with a dissecting aneurysm this goal should be achieved within 5–10 min. In all other patients, this endpoint should be achieved within 1 hour.

32. RAPID BP REDUCTION Acute myocardial ischemia: - IV NTG, b-blockers,ACE inhibitors. CHF with pulmonary edema: - Iv NTG, furosemide, morphine Acute aortic dissection: - Iv nitroprusside +b-blockers or iv trimethaphan b-blockers. Hypertensive encephalopathy or sub-arachnoid hemorrhage: - Iv nitroprusside, labetalol or nimodipine. MAO-tyramine interactions with acute hypertension: - iv phentolamine.

33. Treatment ischemic strokes Only patients with hypertensive emergencies require immediate reduction in markedly elevated blood pressure. In all other patients the elevated blood pressure can be lowered slowly using oral agents. Lowering BP in patients with ischemic strokes may reduce CBF, which because of impaired auto-regulation may result in further ischemic injury. The common practice of 'normalizing' BP following a CVA is potentially dangerous. When a proximal arterial obstruction results in a mild stroke, a fall in blood pressure may result in further infarction involving the entire territory of that artery. Recommendation of the AHA is that hypertension in the setting of acute ischemic stroke should only be treated 'rarely and cautiously'. BP should be carefully observed for the first 1 to 2 hours to determine if it will spontaneously decrease. Only a persistently MAP over 130 mm Hg or a SBP over 220 mm Hg should be carefully treated. In this setting, MAP should be lowered by 15% to 20%.

34. Treatment hemorrhagic strokes In patients with intracerebral hematomas there is almost always a rise in intracranial pressure with reflex systemic hypertension. There is no evidence that hypertension provokes further bleeding in patients with intracranial hemorrhage. However, a precipitous fall in systemic blood pressure will compromise cerebral perfusion. The controlled lowering of the BP is currently recommended only when the systolic blood pressure is greater than 200 mmHg or the diastolic pressure is greater than 110 mmHg AHA recommends treating hypertension in the setting of an intra-cerebral bleed only when blood pressure is more than 180/105 mm Hg. Mean arterial pressure should be maintained below 130 mm Hg. Study demonstrated that the rapid decline in BP within the first 24 hours after presentation was associated with increased mortality in patients with an intracranial hemorrhage. The rate of decline in BP was independently associated with increased mortality

35. Treatment of pregnancy & hypertensive crisis Pregnant patients with hypertensive crises represent a special group of patients. intravenous drug therapy is reserved for those patients with SBP persistently greater than 180 mmHg or DBP persistently greater than 110 mmHg (105 mmHg in some institutions). Before delivery it is desirable to maintain the DBP greater than 90 mmHg because this pressure allows for adequate utero-placental perfusion. If DBP decreases to below 90 mmHg, then decreased utero-placental perfusion may precipitate acute fetal distress progressing to an in utero death or to perinatal asphyxia.

38. PROGNOSIS: Median survival duration is 144 months for all patients presenting to ED with hypertensive emergency. - 5 yr survival rate is 74%.

39. So,………. A 56 yo CM with no significant PMH presents to the ER with headache,found to have BP 210/110mmHg and papilledema. -MALIGNANT HYPERTENSION An 82 yo male with h/o HTN,chronic renal insufficiency presents for a routine physical,found to have BP of 230/130mmHg.-ACCELERATED HYPERTENSION A 76 yo female is brought to the ER by the family due to altered mental status.BP is 240/110 mmHg with no focal neuro findings. –HYPERTENSIVE EMERGENCY

40. Take home points Distinguishing between hypertensive emergency (associated with acute target organ damage) and urgency (no target organ damage) is crucial to appropriate management. Diagnosis of hypertensive emergency requires a thorough history (evidence of target organ damage, illicit drug use, and medication compliance) as well as a complete physical examination, basic laboratory data, and electrocardiogram to assess for the presence of target organ damage and determine its severity. In general, hypertensive urgency is managed using oral antihypertensive drugs in outpatient or same day observational settings, while hypertensive emergency is managed in an intensive care unit or other monitored settings with parentral drugs.

41. Take home points The initial goal in hypertensive urgency is a reduction in mean arterial pressure by no more than 25% within the first 24 hours using conventional oral therapy; in hypertensive emergency, mean arterial pressure should be reduced approximately 10% during the first hour and an additional 15% within the next 2 to 3 hours. Various medications are available for the treatment of hypertensive emergency; specific target organ involvement and underlying patient co-morbidities

42. Thanks for your Attention!

43. SPECIFIC TREATMENT Hypertensive Encephalopathy: Goal is to reduce MAP by not>25% or DBP tp100mmHg in the first hour.Nitroprussi(widely used in past)is a powerful arteriloar dilator,so a rise in ICP may occur.Labetalol,fenoldopam used more now. Intracerebral Hemorrhage: CPP=MAP-ICP.As ICP rises,MAP must rise for perfusion but this raises risk of bleeding from small arteries and arterioles.A prosp. Obs. study in 1997 did not confirm these concerns but it was obscured by early use of anti- hypertensives.Cerebral autoregulation curve in chronic hypertensives may be altered,making them less likely to tolerate aggressive lowering of BP.MAP guidelines:decrease when MAP>130 or SBP>220.Labetalol,esmolol agents of choice. SAH: Nimodipine decreases vasospasm that occurs due to chemical irritation of arteries by blood.Not recommended routinely due to high incidence of hypotension.Cognitive status is a guide.Labetalol,esmolol agents of choice. Acute Ischemic Stroke: High BP can cause hemorrhagic transformation of infarct,cerebral edema.But,if CPP is low,ischemic penumbra may occur.CPP beyond obstn is low.Distal vessels become dilated with,loss of autoregulation.A decilne to pre- stroke values in 4 days has been documented often..A Cochrane review examining 65 RCTs with 11,500 pts. Concluded that insufficient data exists to evaluate BP lowering post-stroke.AHA guidelines:BP be reduced only if SBP>220 or DBP>120mmHg.(unless end-organ damage is due to BP).Labetalol,nitroprusside-agents of choice.For thrombolysis,BP<185/110.

44. FOLLOW-UP The Joint National Committee on High Blood Pressure has published a series of recommendations for appropriate follow-up, assuming no end-organ damage. -For a systolic BP 140-159 mm Hg/diastolic 90-99 mm Hg, confirm BP within 2 months. -For systolic BP 160-179 mm Hg/diastolic 100-109 mm Hg, evaluate within a month. - For systolic BP 180-209 mm Hg/diastolic 110-119 mm Hg, evaluate within a week. -For systolic BP greater than 210 mm Hg/diastolic greater than 120 mm Hg, evaluate immediately.

46. TRIALS HYPERTENSIVE EMERGENCY:1 RCT HYPERTENSIVE URGENCY:10 RCTS. CONCLUSIONS:-Evidence about effectiveness of antihypertensive agents in people with hypertensive emergencies or hypertensive urgencies is weak. Studies had small sample sizes and were heterogeneous in terms of patients, interventions and outcomes reported. Limited evidence suggests that urapidil is most effective in emergencies. In urgencies, nicardipine; nitroprusside or fenolodopam may be used, but not nifedipine.

47. Normally autoregulation maintains a constant blood flow between MAP 50 mmHg and 150 mmHg. However in traumatised or ischaemic brain, or following vasodilator agents (volatile agents and sodium nitroprusside) CBF may become blood pressure dependent. Thus as arterial pressure rises so CBF will rise causing an increase in cerebral volume. Similarly as pressure falls so CBF will also fall, reducing ICP, but also inducing an uncontrolled reduction in CBF.