Severe Hypertension: In a Clinical Pearls Format

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Severe Hypertension In a Clinical Pearls Format

• Gregory W. Rutecki, M.D.,
• Bradley M. Wright, Pharm. D., BCPS, Molly Adams
  Pharm. D., BCPS, U.niversity of S.outh A.labama
  Auburn University

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What is a Clinical Pearls Format?

• At the 2001 American College of Physicians
  Annual Conference, a new teaching format to aid
  physician learning, Clinical Pearls, was
  introduced. Understanding 3 qualities of
  physician learners allowed the design of Clinical
  Pearls to be created. First, physicians learn
  from cases. Second they like practical points
  they can use in their practice. Finally,
  physicians take pleasure in problem solving.
• Mayo Clin. Proc. 2010851046-1050.

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The Format

• A number of short cases dealing with severe
  hypertension (180 or gt mm/hg systolic//110 or gt
  diastolic) will be presented.
• A multiple choice question will follow each.
• Clinical Pearls will be furnished. They are
  defined as practical teaching points supported by
  the literature/evidence.
• This format has become one of the most popular
  sessions at the National ACP.

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CASE 1.

• A 43-year-old black man presents to the Emergency
  Department with a blood pressure of 240/162
  mm/hg.
• Physical Examination did not include a
  funduscopic examination.
• He is started on a nitroglycerin drip admitted
  as a hypertensive urgency.
• Previous BUN/Creatinine values were 20/1.3
  mg/dl., now they have increased precipitously to
  132/11.3 mg/dl for unknown reasons.
• A new normocytic anemia schistocytes acute
  renal failure are present.

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Question for Case 1

• Which of the following choices is most correct?
• a.) Information in the case presentation suggests
  the patient has a hypertensive emergency.
• b.) nitroglycerin is the correct therapy.
• c.) a funduscopic will not add much to the acute
  evaluation.
• d.) In his situation, the distinction between
  urgency and emergency is not critical.

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Presence or Absence of Target Organ Injury is the
Key

• The Fundus
• Cardiovascular System
• Brain
• Hematology
• Kidney

• Grade 3 4 hypertensive retinopathy.
• An ischemic syndrome, failure, or dissection of
  the aorta
• Caveats with ischemic strokes a possible future
  change in hemorrhagic strokes. Do you know about
  PRES or Posterior Reversible Encephalopathy?
• Remember the BAD old days of scleroderma and
  schistocytes?

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Where have all the Ophthalmoscopes gone?

• Confessions of a midnight Ophthalmologist

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Lets look at the excuses

• MYTH Mydriatic drops can precipitate acute
  narrow angle glaucoma (Angels and Ministers of
  Grace Defend us!!!)

• BMJ studies comprised by 6760, 4870, 3654
  persons dilated randomly 0.03, 0, and 0
  developed narrow angle glaucoma.
• Systematic Review 600,000 patients--risk of
  glaucoma was 1 in 20,000.
• 13 studies wherein persons WITH NARROW ANGLE
  GLAUCOMA given drops, not one developed narrow
  angle closure

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Malignant Hypertension//Hypertensive Emergency
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CP1098816-1
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Case 1 Clinical Pearl

• It is NOT the blood pressure per se that
  determines urgency versus emergency, BUT
  RATHER whether severe hypertension (gt180/gt110
  mm/hg) is associated with target organ
  damage/injury. The most accessible site for the
  clinician to uncover that damage is the fundus.

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Eight days in the ICU what do you get, (not a
little bit older.debt)

• Blood Pressure in a 28 y.o. of 200s/130s mm/Hg.
• Treated as a stubborn urgency in the ICU,
  meaning that it took 8 days of concoctions
  (hydralazine and labetalol) to reach a semblance
  of control.
• Transferred to floor and a funduscopic is
  performed. Grade 3 hypertensive retinopathy
  (hemorrhages and exudates) is discovered after
  dilatation.
• He has acute on chronic renal failure
  (BUN/Creatinine 46/4.7 from 30/2.8 mg/dl) and
  schistocytes.

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Clinical Case 2, question

• If the hypertensive emergency was discovered
  earlier which agent below would have been the
  most appropriate therapy?
• A.) hydralazine parenterally
• B.) clonidine loading
• C.) fenoldopam
• D.) nitroprusside
• E.) nitroglycerin

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The Righteous Brothers were right Time does go
by slowly

• We have come a long way from diazoxide,
  nitroprusside, clonidine, nitroglycerin,
  hydralazine.
• Our vocabulary must include nicardipine,
  labetalol, clevidipine, fenoldopam.
• Lets look at some subtractions some additions
  to the severe hypertension armamentarium

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Lets look at Fenoldopam

• How does it work?
• It is a peripheral dopamine type-1 receptor
  agonist dilating coronary, renal, mesenteric,
  peripheral arteries. An gt in renal blood flow
  GFR can be seen with fenoldopam. Studies
  comparing fenoldopam to nitroprusside in the
  setting of hypertensive emergencies have
  demonstrated NO DIFFERENCE in time to goal blood
  pressure or attainment of mean arterial pressure.
  Studies post-cardiac surgery have reported
  improved outcomes with fenoldopam over both
  nifedipine and nitroprusside after CABG. AVOID
  with neurological injury glaucoma.

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Lets look at Hydralazine/nitroglycerin -- /--

• How do they work?
• Hydralazine direct arterial vasodilator. Onset
  of action 5-15 minutes, BUT its pharmacological
  effect can last up to gt12 hours! In coronary
  disease/dissection, it can worsen the
  cardiovascular situation! It can RAISE
  intracranial pressure. To our OB colleagues
  meta-analysishydralazine increases maternal
  hypotension c-sections, placental abruptions,
  is associated with lower Apgar scores.
• Nitroglycerin for hypertensive emergency when
  the TOD/I is heart (ischemia, failure), but
  exacerbates volume depletion hypotension and
  gtICP.

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Lets look at clevidipine labetalol,

• Clevidipine, How does it work?
• Short acting Ca Channel Blocker with utility in
  multiple settings except aortic stenosis, heart
  failure, egg and soybean allergy.
• Labetalol alpha-1 beta antagonist. Across the
  board and no fetal distress.
• Know about phentolamine, nicardipine, esmolol

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Clinical Pearl 2 Tailor made medications

• Haas AR. Marik PE. Current Diagnosis and
  management of Hypertensive Emergency. Seminars In
  Dialysis 2006 19502-12.
• 1.) Myocardial ischemia/encephalopathy
• LABETALOL
• 2.) Acute/chronic renal failure
• FENOLDOPAM
• 3.) Pregnancy
• LABETALOL
• 4.) Aortic dissection
• ESMOLOL
• 5.) Sympathetic crisis
• NICARDIPINE (phentolamine)

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Cognizance of Systems Safety

• Improving quality and safety of hospital care a
  reappraisal an agenda for clinically relevant
  reform. Internal Medicine Journal 2008 3844-55.
• Prevention of Medication errors Actively involve
  clinical pharmacists in the medication use
  process through attendance on ward rounds

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Case 3 an ambulatory person with resistant
hypertension

• Definitions, work up, and therapy

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Case 3 Resistant, ambulatory hypertension

• A 54 y.o. Latino man with DM2 and OSA sees you in
  the office for a blood pressure of 210/140 mm/hg.
• His BP management is enalapril 20 mg/day.
• He has no target organ damage/injury on
  examination.
• He brings screening laboratory work Na 141, K
  1.8, Cl- 99, HCO3 51 meQ/L respectively.
• ABGs pH 7.59, paO2 50 mm/Hg, pCO2 51 mm/Hg
• Urine lytes (SPOT) Na 46, K48, Cl- 84 meQ/L
  respectively.

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Question, Case 3

• Which of the following statements regarding
  resistant hypertension is most accurate (we will
  revisit case 3, step by step after you answer)
• a.) The definition of resistant hypertension is
  failure to control after adherence with a 4 drug
  regimen.
• b.) beta blockers consistently lower blood
  pressure across all demographic groupings.
• c.) Maxing out monotherapy is superior to
  multiple drugs at lower doses.
• d.) Aldosterone/renin levels are a valuable
  adjunct in the evaluation of the resistant
  hypertensive.

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Debunking a Myth beta blockers are good
antihypertensives (defining a good regimen).

• Brewster L.M., van Montfrans G.A., Kleijnen J.
  Systematic Review Anti-hypertensive Drug Therapy
  in Black Patients. Ann. Intern. Med. 2004 141
  614-627.
• 1.) B-Blockers did not differ significantly from
  placebo in reducing systolic blood pressure as
  monotherapy in blacks.
• 2.) Two Other studies (Br Med J/Jamaica Curr.
  Med. Res. Opin./A.A.) found that both selective
  and non-selective b-blockers increased blood
  pressure relative to placebo in up to 38 of
  participants.
• (n 8,300/BP LVH) composite end points of
  stroke, MI, CVD death was 13 less frequent in
  the losartin group compared to the b-blocker
  group

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The beta blocker moratorium continued

• ASCOT-BPLA (n 20,000) atenolol vs. amlodipine,
  stopped early because of a 11 lower all-cause
  mortality in the amlodipine limb.
• J. Am. Coll. Cardiol. 2009 Hindbrain belief
  that tachycardia beta blocker. NO, unless there
  is heart failure or another Evidence-based
  rationale.
• 6 trials/ 55,675 pts./ B-blockers conferred a
  31 increased risk of new diabetes vs. placebo
  11 vs. other antihypertensives. The DM persons
  had a gt3x increase in CVD. In GEMINI, this
  specific risk (DM) was mitigated by using
  carvedilol instead of a pure beta-blocker.

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Conclusions

• Titration of beta blockers in treating
  hypertension, B-blockade-induced bradycardia
  (80,000 pts. in 9 trials) the lower the heart
  rate, the higher the CV mortality, M.I.s,
  strokes, and incidence of HF!!!!
• AND ALLHAT (gt10,000 A.A.) A.A. randomized to a
  ACEI mono had a 40 greater risk of stroke, a 32
  greater risk of of HF, and a 19 greater risk of
  CVD than those randomized to a diuretic.

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Resist the urge to Max out monotherapy!

• Wald D.S., Law M., Morris J.K., et. al.
  Combination Therapy versus Monotherapy in
  Reducing Blood Pressure Meta-analysis on 11,000
  Participants from 42 Trials. Am J Med. 2009 122
  290-300.
• N 10,968
• Doubling the dose of one drug (or monotherapy)
  had approximately one-fifth of the equivalent
  incremental blood pressure lowering effect of
  adding another drug class before trying to
  max-out.
• CAVEATS 50 mg hctz or combination diuretics!
  (MAXIDER, for example).

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Love those guys Renin and aldosterone

• Lane et. al. (J Hypertens 2007 25 891-894.).
  133 patients with resistant hypertension
  spironolactone SBP decline 21.7 mm/Hg DBP
  decline 8.5 mm/Hg.
• Sens. Spec. PV --PV
• ARR gt20 78 83 56 93
• ARR gt50 10 99 86 80
• ARR gt20
• 57 88 57
  88
• PAC gt15

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Back to Case 3

• Is he resistant? No, he would have required
  treatment failure on a good 3 drug regimen.
• Is he a hypertensive emergency?
• Why does he have hypokalemia, alkalemia, a high
  urine chloride?
• His aldosterone-renin values were 6 .8.
• Apparent mineralocorticoid excess His cortisol
  was elevated.
• His ACTH was sky high adrenals were massive
  so?

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Clinical Pearl(s)

• When patients fail on a well thought out 3 drug
  regimen, they need a workup (OSA?).
  Aldosterone-renin profiling is a valuable
  adjunct. Be circumspect when prescribing
  beta-blockers for hypertension.
• A future pearl All patients with hypertension
  may be renin profiled and treated accordingly.
• Thank you.