HYPERTENSION. Background for understanding the Hypertension literature. Case presentation. Approach to Treatment. Jeffrey J. Kaufhold, MD Nephrology

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1 HYPERTENSION Background for understanding the Hypertension literature. Case presentation Approach to Treatment Jeffrey J. Kaufhold, MD Nephrology 2009

2 HYPERTENSION SUMMARY 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 Awareness Treatment Control

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 Flame hemorrhage Keith and Wagoner, 1974 Cotton wool spot papilledema

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

21 Malignant Hypertension 37 y.o. male with severe htn and ESRD presents with mental status changes, dysarthria, and BP of 250/170 Treated with Nipride to target BP of 200/100 2 days later, he develops agitation, tachycardia, hypotension. Anion Gap is increased.

22 Nipride Toxicity Limited by what toxicity? Who is at risk for this toxicity? Symptoms of toxicity? Treatment of Toxicity?

23 Malignant Hypertension Cyanide Toxicity Thiocyanate toxicity presents the same. To avoid this you can: Get them off Nipride ASAP, by immediately resuming outpt oral meds (I like q6h procardia XL) Use another agent, such as Nitroglycerine, Labetolol drip. Expensive option is Corlepam.

24 Treatment of Cyanide Toxicity due to Nipride administration Discontinue sodium nitroprusside administration. Buffering the cyanide by using sodium nitrite to convert haemoglobin to methaemoglobin as much as the patient can safely tolerate. 3% sodium nitrate (5 mg/kg over 5 min), which oxidizes hemoglobin to methemoglobin, which interferes with cyanide permanently bonding to the hemoglobin molecule Infusing sodium thiosulfate to convert the cyanide to thiocyanate. Administering sodium thiosulfate (150 mg/kg over 15 min). Thiocyanate is still toxic, but reversibly binds, and clears with time.

25 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)

26 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

27 Malignant Hypertension I.V. Treatment: Nicardipine drip 5-15 mg/hr Longer half-life so slower titration and won t clear rapidly

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

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

30 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

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

32 Hypertension Literature Summary Malignant Hypertension Kincaid-Smith and others DBP > 130 VA Cooperative Studies DBP mm Hg DBP mm Hg

33 HYPERTENSION Literature Summary US Public Health Service 1977 Prospective placebo controlled trial for DBP 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.

34 Stepped Care approach to treatment of HTN, 1979 Step 1: start Either B-Blocker or Thiazide diuretic Step 2: start Thiazide or B-Blocker Step 3: Add Hydralazine (what they had at the time) (or add any vasodilator, like Amlodipine, Nifedipine, Doxazozin, Felodipine etc Step 4: Add Centrally acting agent like Aldomet, at the time they had Guanabenz/ Guanethidine. could use Clonidine Step 5: Add Minoxidil

35 HYPERTENSION PARALLEL 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 LRC (Lipid Research Clinics) Treatment of hyperlipidemia reduced risk of heart disease, all-cause mortality not effected.

36 HYPERTENSION Recent 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 VA Cooperative Study, Materson, NEJM Compares 6 agents. Efficacy in 55 % range. Drug intolerance 6 to 14 %.

37 Joint National Commission JNC founded on HDFP JNC Intro of ACE, alpha B. JNC Special situations JNC Many agents 1 st line JNC Back to stepped care. JNC ACE for Diabetics JNC

38 Joint National Commission 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) From JAMA

39 HYPERTENSION JNC 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."

40 HYPERTENSION JNC VII Outline Epidemiology of HTN Evaluation of HTN NON Pharmacologic treatments: Wt loss, diet, exercise, alcohol Drug treatment Special Issues in HTN

41 Stages of Hypertension Normal < 120 / 80 Prehypertension / Stage / Stage 2 > 160 / >100

42 Treatment of Hypertension Single agent HCTZ or Chlorthalidone 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

43 Classes of Antihypertensives Diuretics Rate control agents BBlocker, Verapamil, Diltiazem ACE/ ARB s Vasodilators Dihydropyridines, Hydralazine, Alpha blockers, Minoxidil Central agents: clonidine, aldomet. Nephrologist Tricks: Spironolactone, Phenoxybenzamine mg BID

44 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)

45 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.

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