Understanding Malignant Hypertension | Treatment Approach and Case Studies

1. HYPERTENSION Background for understandingthe Hypertension literature. Case presentation Approach to Treatment Jeffrey J. Kaufhold, MDNephrology 2009

2. HYPERTENSIONSUMMARY • Background for understanding the literature of Hypertension • Review of Joint National Commission Recommendations (VII) 2003 • Clinical Evaluation and Case histories.

3. Nat’l Health & Nutrition Exam Survey NHANES JNC 7 Dec 2003

4. Case Presentation • 56 y.o. A.A. male prior weight lifter presents for refractory HTN. • Normal labs and UA. Normal CXR and EKG. • Meds: Clonidine 0.2 BID • ACE inhibitor • Diltiazem 300 mg daily

5. Case Presentation • Physical Exam: • BP 170 / 110 Pulse 85 • Edema 2 +

6. Case Presentation • Special populations help define your approach. • African Americans: • CHF • Diabetics:

7. Case Presentation • Special populations help define your approach. • African Americans: Volume Mediated, Low renin low Aldo. • CHF: ACE, Diuretics, B-blocker • Diabetics: ACE or ARB.

8. Case Presentation • 56 y.o. A.A. male with edema, HTN • Normal labs and UA. Normal CXR and EKG. • Meds: Clonidine 0.2 BID • ACE inhibitor • Diltiazem 300 mg daily • Whats Missing???

9. Case Presentation • 56 y.o. A.A. male with refractory HTN. • Meds: Clonidine 0.2 BID • ACE inhibitor - Stopped • Diltiazem 300 mg daily • I added HCTZ 50 mg daily.

10. Case Presentation • 56 y.o. A.A. male with refractory HTN. • Meds: Clonidine 0.2 BID • Diltiazem 300 mg daily • HCTZ 50 mg daily. • Still swelling, BP a little better. 156 / 100.

11. Case • 56 y.o. AA male with refractory HTN. • I changed diuretics to Lasix and Zaroxolyn. • I get a call 3 days later: Swellings gone, but I can’t get out of bed – too dizzy!

12. Case Presentation • 56 y.o. A.A. male with refractory HTN. • Meds: Lasix 40 mg BID • Zaroxolyn 5 mg weekly • No swelling, BP 126 / 80. • Pt reports joint pain and swelling. What test do you order next?

13. Case • Uric acid level is 12 • Creatinine 1.4 • K 3.8 • Glucose 244 (nonfasting)

14. Case • Pt stopped his meds due to the pain, and symptoms improved. • BP climbed to 200/110 • Headaches, visual blurring, DOE, dizzy.

15. Malignant HTN • Mortality of 50% within 2 years! • Usual mode of exit was Heart Failure, stroke or Renal failure. • Marked by severe hypertension with end organ damage • Hypertensive emergency = high BP with sx • Hypertensive urgency= high BP no sx.

16. Malignant HTN • End Organ Damage: • Renal failure • CHF with Pulmonary Edema • Stroke (esp with bleeding), Encephalopathy • Retinopathy • Flame Hemorrhages, Papilledema

17. Malignant HTN • End Organ Damage: Retinopathy Cotton wool spot papilledema Flame hemorrhage Keith and Wagoner, 1974

18. Malignant Hypertension • Treatment Goals: • Get BP down to safe level, not “normal” • (brain needs to autoregulate blood flow) • Target 25 % reduction or SBP < 170, DBP<105 within 6 hours. • Control symptoms, especially SOB, CP

19. Malignant Hypertension • Treatment Principles: • ICU monitoring • consider Art line if cuff BP readings are suspect. • Use agents which are safe and rapidly titratable depending on response • Get pt OFF IV therapy as soon as possible and on Oral meds.

20. Malignant Hypertension • I.V. Treatment: • Nipride drip Start 0.25 to 0.5 microgm/kg/min up to 2 mcg/kg/min • max dose about 8 mcg/kg/min • Limited by what toxicity? • Who is at risk for this toxicity? • Symptoms of toxicity? • Treatment of Toxicity?

21. Malignant Hypertension • I.V. Treatment: • Nitroglycerine drip 5 mcg/min (no kg in here) up to 100 mcg/min (have gone as high as 200 in some cases) • Same dose for Angina, (preferred treatment in cases with CP)

22. Malignant Hypertension • I.V. Treatment: • Labetolol drip give 20 mg IV slow push, followed by drip at 0.5 to 2 mg/min • use with caution in pts with bradycardia, CHF, Asthma, Crystal Meth use • Probably treatment of choice in pt with B-blocker withdrawal syndrome

23. Malignant Hypertension • I.V. Treatment: • Nicardipine drip 5-15 mg/hr • Longer half-life so slower titration and won’t clear rapidly

24. Malignant Hypertension • I.V. Treatment: • Esmolol drip (Brevibloc) 80 mg IVP followed by 150-300 mcg/kg/min infusion • useful for suppression of arrhythmias, use in OR with anesthesia

25. Malignant Hypertension • I.V. Treatment: • Corlepam/fenoldepam dopamine congener • start at dose of 0.1 mcg/kg/min titrate up to 1-2 mcg/kg/min as needed • contraindicated in pt with glaucoma. • Preserves Renal Perfusion • Expensive!

26. Malignant Hypertension • I.V. Treatment: • Phentolamine 5-15 mg IV bolus every 5-15 min • or drip of 1 mg/min • Alpha blockade, so especially useful in cases with pheochromocytoma, Tyramine-Cheese reaction with MAO-inhibitor

27. Case • Started Allopurinol for gout. • Pt started exercising and watching diet. • Sugars normalized without treatment.

28. HypertensionLiterature Summary • Malignant Hypertension - 1958 Kincaid-Smith and others DBP > 130 • VA Cooperative Studies - 1967 DBP 115-129 mm Hg - 1970 DBP 90 -114 mm Hg

29. HYPERTENSIONLiterature Summary • US Public Health Service 1977 Prospective placebo controlled trial for DBP 90-115 mm Hg • HDFP 1979 Introduced concept of Stepped Care • Oslo Study 1980 Treatment of Mild Hypertension • Medical Research Clinics (MRC) 1985 Single blind and community based.

30. HYPERTENSIONPARALLEL WORK • 1948 to 1972 Framingham Study 20 year follow-up on 5000 pts • 1982 MRFIT Randomized primary prevention trial Lower than expected rate of mortality in controls led to NS reduction. • 1984 LRC (Lipid Research Clinics) Treatment of hyperlipidemia reduced risk of heart disease, all-cause mortality not effected.

31. HYPERTENSIONRecent Works • 1985 HDFP follow-up Study Long term surveillence for drug side effects: 9-25 % • 1992 Gurwitz Ann Int Med Antihypertensive therapy and the initiation of Tx for DM. Diabetes and HTN are linked, drugs and diabetes are NOT. • 1993 VA Cooperative Study, Materson, NEJM Compares 6 agents. Efficacy in 55 % range. Drug intolerance 6 to 14 %.

32. Joint National Commission • JNC 1 1980 founded on HDFP • JNC 2 1984 Intro of ACE, alpha B. • JNC 3 1986 Special situations • JNC 4 1988 Many agents 1st line • JNC 5 1993 Back to stepped care. • JNC 6 1997 ACE for Diabetics • JNC 7 2003

33. HYPERTENSIONJNC V • "Because diuretics and B-Blockers are the only classes of drugs that have been used in long-term controlled trials and shown to reduce morbidity and mortality, they are recommended as first- choice agents unless they are contraindicated or unacceptable, or unless there are special indications for other agents."

34. HYPERTENSIONJNC VII Outline • Epidemiology of HTN • Evaluation of HTN • NON Pharmacologic treatments: Wt loss, diet, exercise, alcohol • Drug treatment • Special Issues in HTN

35. Normal Prehypertension Stage 1 Stage 2 < 120 / 80 120 -139 / 80-89 140-159 / 90-99 > 160 / >100 Stages of Hypertension

36. Treatment of Hypertension • Single agent – HCTZ for most pts. B-Blocker for females/ high heart rate. • Stage 2 I start with DHP CCB (procardia XL) • plus one or both of above. • Resistant HTN I look for CLASSES of agents

37. Classes of Antihypertensives • Diuretics • Rate control agents BBlocker, Verapamil, Diltiazem • ACE/ ARB’s • Vasodilators Dihydropyridines, Hydralazine, Alpha blockers, Minoxidil • Central agents: clonidine, aldomet.

38. Nephrology level htn • I tell the pt that will need to control the main route plus the main detours causing the HTN. • Rate control (pulse < 78) • Diuretic • Vasodilator DHP CCB, Hydralazine, Cardura, Minoxidil. • ACE / ARB (accept 30% increase in creat if BP responds)

39. Refer to Nephrologist • If unable to control on 3 drug regimen which includes Rate control, diuretic. • If you are considering Minoxidil • If creatinine climbs more than 30 % or if creatinine is over 2.0.