1. Hypertensive Emergencies Phillip D. Levy, MD, MPH, FACEP Associate Professor Associate Director of Clinical Research Wayne State University Department of Emergency Medicine

2. Relevant Disclosures Grant/Research Support –The Robert Wood Johnson Foundation Physician Faculty Scholars Program, the NIH Loan Repayment Program (Health Disparities Division), and the NIH/NIHMD (1R01 MD005849-01A1) Consultant –The Medicines Company, EKR Therapeutics

3. Purpose of This Lecture To provide an overview of the “what” and “why” of contemporary ED management of acute HTN –Utilize an evidence-based discussion format –Focus on differentiation between simple BP elevation and true hypertensive emergency

4. Why This Topic? Nawar et al. Adv Data 2007; 386:1-32.

5. Why This Topic? Pitts et al. Natl Health Stat Report 2008;7:1-38.

6. Based on JNC VII Class http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm

7. Reflects the General Population Prevalence Lloyd-Jones et al. Circulation 2010;121;e1-e170.

8. As Well As Racial and Ethnic Demographics Lloyd-Jones et al. Circulation 2010;121;e1-e170.

9. And Low Levels of Awareness, Treatment and Control Lloyd-Jones et al. Circulation 2010;121;e1-e170.

10. So The BP is High - Now What ? http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm

11. So The BP is High - Now What ? http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm

12. So The BP is High - Now What ? http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm

13. Shayne and Pitts. Ann Emerg Med. 2003;41:513-29.

14. Are All of These Patients the Same? Kessler and Joudeh. Am Fam Physician. 2010;81:470-76.

15. Clearly Not! Kessler and Joudeh. Am Fam Physician. 2010;81:470-76.

16. What Constitutes a Hypertensive Emergency? 1,2 1 Varon and Marik. Chest 2000;118:214-27. 2 Rynn et al. J Pharm Prac 2005;18:363-76.

17. Pathophysiology of a Hypertensive Emergency 1,2 1 Ault and Ellrodt. Am J Emerg Med 1985; (suppl 6):10-15. 2 Varon and Marik. Chest. 2000;118:214-27.

18. Chirinos and Segers. Hypertension 2010;56:563-70.

19. Kawaguchi et al. Circulation 2003;107:714-20. Macrocirculatory: Arterial Impedance

20. What End-Organs Are Typically Involved? Zampaglione et al. Hypertension 1996;27:144–7.

21. Katz et al. Am Heart J 2009;158:599-606.

22. Patient Outcomes

23. Szczech et al. Circulation 2010;121:2183-91.

24. Deshmukh et al. Am Heart J. 2011 [epub ahead of print].

25. Stead et al. Neurology 2005;65:1179-83.

26. Gheorghiade et al. JAMA 2006;296:2217-26.

27. Perez et al. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD003653.

29. Adrenergic receptor blockers –Esmolol ( β 1 ) –Labetalol ( α 1 and β ) –Phentolamine ( α 1 ) –Urapidil ( α 1 ) Ca 2+ channel blockers –Nicardipine –Clevidipine ACE inhibitors –Enalaprilat Treatment Typically Parenteral NO donors –Nitroprusside –Nitroglycerin –Isosorbide dinitrate NP analogue –Nesiritide Dopamine agonist –Fenoldopam Direct vasodilator –Hydralazine

30. Katz et al. Am Heart J 2009;158:599-606. What Is Used Most Commonly?

31. Katz et al. Am Heart J 2009;158:599-606. How Well Does That Work?

32. Katz et al. Am Heart J 2009;158:599-606. Differential Antihypertensive Response

33. Blood Pressure Dynamics MAP = DBP + ([SBP - DBP]/3) MAP = (CO x SVR) + CVP –CO = HR x SV

34. Reference: Peacock et al. Peacock et al. Critical Care 2011 [epub ahead of print].

35. Reference: Peacock et al. CLUE Study Evaluation of Intravenous niCardipine and Labetalol Use in the Emergency Department CLUE Study Evaluation of Intravenous niCardipine and Labetalol Use in the Emergency Department Peacock et al. Critical Care 2011 [epub ahead of print].

36. Reference: Peacock et al. CLUE Study Evaluation of Intravenous niCardipine and Labetalol Use in the Emergency Department CLUE Study Evaluation of Intravenous niCardipine and Labetalol Use in the Emergency Department Peacock et al. Critical Care 2011 [epub ahead of print]. Final multivariable logistic regression model †* for “met target SBP within first 30 minutes”

37. Rhoney and Peacock. Am J Health-Syst Pharm. 2009; 66:1343-52. Specific Indications

38. How Low Should You Go? Simple answer –25% reduction in MAP within 1 st hour –Target ~ 160/100 mm Hg by 2-6 hours Marik and Varon. Critical Care 2003, 7:374-84.

39. How Low Should You Go? Better answer –It really depends on clinical condition Less aggressive with ischemic stroke More aggressive with hemorrhagic stroke, acute HF and aortic dissection

40. Aiyagari and Gorelick. Stroke 2009;40:2251-56. AHA/ASA Recommendations for BP Management in AIS

41. Aiyagari and Gorelick. Stroke 2009;40:2251-56. AHA/ASA Recommendations for BP Management in AIS

42. Aiyagari and Gorelick. Stroke 2009;40:2251-56. AHA/ASA Recommendations for BP Management in AIS

43. Aiyagari and Gorelick. Stroke 2009;40:2251-56. AHA/ASA Recommendations for BP Management in ICH

44. Aiyagari and Gorelick. Stroke 2009;40:2251-56. AHA/ASA Recommendations for BP Management in ICH

45. Sandset et al. Lancet 2011 [epub ahead of print].

48. Impact of Early Reduction Rhoney et al. Presented at the 2011 Neuro-Critical Care Society Meeting.

49. Impact of Early Reduction Rhoney et al. Presented at the 2011 Neuro-Critical Care Society Meeting.

50. Anderson et al. Stroke 2010;41:307-12. Guideline: SBP < 180 mm Hg Intensive: SBP < 140 mm Hg

51. Anderson et al. Lancet Neurol 2008;7:391–9. But No Direct Clinical Benefit at 90 Days…

52. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) investigators Crit Care Med 2010;38:637-48.

54. Qureshi et al. Arch Neurol. 2010;67:570-6. Hematoma Expansion Modified Rankin Scale Score

55. Qureshi et al. Arch Neurol. 2010;67:570-6.

56. Liu-DeRyke et al. Neurocrit Care 2008;9:167-76. BP Goal by 1 hr: 11% vs. 56% (p=0.02)

57. Stead et al. Neurology 2006;66:1878–81. n=51n=20

58. Hunt et al. Circulation. 2009;119(14):e391-479. AHA/ACC Recommendations for BP Management in Acute HF

59. What About the Rest? Kessler and Joudeh. Am Fam Physician. 2010;81:470-76.

60. Pitts and Adams. Ann Emerg Med 1998;31:214-8.

61. Grassi et al. J Clin Hypertens 2008;10:662–7.

62. BP Response to Rest Grassi et al. J Clin Hypertens 2008;10:662–7.

63. Retrospective Cohort Study ED Visit 24 Hrs, n (%)14 (2.4)19 (4.4)0.082 ED Visit 24 Hrs Due to HTN, n (%)7 (1.2)12 (2.8)0.070 Hospital Admission within 24 Hrs, n (%)0 (0.0)3 (0.7)0.450 Complication at 24 Hrs Due to HTN, n (%)0 (0.0)1 (0.2)0.248 ED Visit within 30 d, n (%)88 (15.2)82 (18.9)0.118 ED Visit within 30 d Due to HTN, n (%)30 (5.2)36 (8.3)0.046 ED visit within 30 d for antihypertensive refill, n (%)10 (1.7)11 (2.5)0.371 Hospital Admission within 30 d, n (%)15 (2.6)13 (3.0)0.695 Complication within 30 d Due to HTN, n (%)6 (1.0)11 (2.5)0.066 ED Visit within 90 d, n (%)95 (16.4)89 (20.5)0.092 ED Visit within 90 d Due to HTN, n (%)41 (7.1)44 (10.1)0.082 ED visit within 90 d for antihypertensive refill, n (%)10 (1.7)12 (2.8)0.261 Hospital Admission within 90 d, n (%)17 (2.9)23 (5.3)0.056 Complication within 90 d Due to HTN, n (%)13 (2.2)14 (3.2)0.336 Death within 30 d, n (%)1 (0.2) 0.837 Death within 1 year, n (%)9 (1.6)9 (2.1)0.534 Untreated n = 581 Treated n = 435 p-value Levy et al. Accepted for poster presentation at ACEP Scientific Assembly 2011 (San Francisco, CA).

64. Wrap Up Critical first step is to differentiate true emergencies from poorly controlled chronic hypertension Intervention for emergencies should be driven by condition-specific goals –Involve more than just a number! –Equate with problems caused by acute HTN –Best achieved using co-morbidity congruous agents