background for understanding the hypertension literature...

HYPERTENSION

Background for understanding the Hypertension literature.

Case presentation

Approach to Treatment

Jeffrey J. Kaufhold, MD Nephrology

2009

HYPERTENSION SUMMARY

●  Background for understanding the literature of Hypertension

●  Review of Joint National Commission Recommendations (VII) 2003

●  Clinical Evaluation and Case histories.

Nat’l Health & Nutrition Exam Survey NHANES

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76-80 88-91 91-94 99-2000

Awareness

Treatment

Control

JNC 7 Dec 2003

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

Case Presentation

Physical Exam: BP 170 / 110 Pulse 85 Edema 2 +

Case Presentation

Special populations help define your approach.

African Americans: CHF Diabetics:

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.

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???

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.

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.

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!

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?

Case

Uric acid level is 12 Creatinine 1.4 K 3.8 Glucose 244 (nonfasting)

Case

Pt stopped his meds due to the pain, and symptoms improved.

BP climbed to 200/110 Headaches, visual blurring, DOE, dizzy.

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.

Malignant HTN

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

Malignant HTN

End Organ Damage: Retinopathy

Keith and Wagoner, 1974

Flame hemorrhage Cotton wool spot papilledema

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

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.

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

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.

Nipride Toxicity

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

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.

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.

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)

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

Malignant Hypertension

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

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

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!

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

Case

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

Hypertension Literature 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

HYPERTENSION Literature 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.

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

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.

●  1984 LRC (Lipid Research Clinics) Treatment of hyperlipidemia reduced risk of heart disease, all-cause mortality not effected.

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.

●  1993 VA Cooperative Study, Materson, NEJM Compares 6 agents. Efficacy in 55 % range. Drug intolerance 6 to 14 %.

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

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

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."

HYPERTENSION JNC VII Outline

●  Epidemiology of HTN

●  Evaluation of HTN

●  NON Pharmacologic treatments: Wt loss, diet, exercise, alcohol

●  Drug treatment

●  Special Issues in HTN

Stages of Hypertension

Normal Prehypertension Stage 1 Stage 2

< 120 / 80 120 -139 / 80-89 140-159 / 90-99 > 160 / >100

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

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 10-40 mg BID

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)

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.