Hypertensive Emergencies: Optimal Therapy in the ED by rQTp26

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									Hypertensive Emergencies


             Phillip D. Levy, MD, MPH, FACEP
                    Associate Professor
          Associate Director of Clinical Research
 Wayne State University Department of Emergency Medicine
       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
   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
Why This Topic?




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




          Pitts et al. Natl Health Stat Report 2008;7:1-38.
Based on JNC VII Class




          http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm
 Reflects the General
Population Prevalence




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




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




                 Lloyd-Jones et al. Circulation 2010;121;e1-e170.
So The BP is High - Now What ?




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




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




              http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm
Shayne and Pitts. Ann Emerg Med. 2003;41:513-29.
Are All of These Patients
        the Same?




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




      Kessler and Joudeh. Am Fam Physician. 2010;81:470-76.
    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.
  Pathophysiology of a
Hypertensive Emergency1,2




             1 Ault  and Ellrodt. Am J Emerg Med 1985; (suppl 6):10-15.
             2   Varon and Marik. Chest. 2000;118:214-27.
Chirinos and Segers. Hypertension 2010;56:563-70.
Macrocirculatory:
Arterial Impedance




            Kawaguchi et al. Circulation 2003;107:714-20.
What End-Organs Are
 Typically Involved?




            Zampaglione et al. Hypertension 1996;27:144–7.
Katz et al. Am Heart J 2009;158:599-606.
Patient Outcomes




            Katz et al. Am Heart J 2009;158:599-606.
Szczech et al. Circulation 2010;121:2183-91.
Deshmukh et al. Am Heart J. 2011 [epub ahead of print].
Stead et al. Neurology 2005;65:1179-83.
Gheorghiade et al. JAMA 2006;296:2217-26.
Perez et al. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD003653.
Perez et al. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD003653.
Treatment Typically Parenteral
• Adrenergic receptor        • NO donors
  blockers                     – Nitroprusside
  –   Esmolol (β1)             – Nitroglycerin
  –   Labetalol (α1 and β)     – Isosorbide dinitrate
  –   Phentolamine (α1)      • NP analogue
  –   Urapidil (α1)            – Nesiritide
• Ca2+ channel blockers      • Dopamine agonist
  – Nicardipine                – Fenoldopam
  – Clevidipine              • Direct vasodilator
• ACE inhibitors               – Hydralazine
  – Enalaprilat
What Is Used Most Commonly?




                  Katz et al. Am Heart J 2009;158:599-606.
             How Well Does That Work?
                                                           One           Two         Three or more

                               Labetolol (n=501)     32%                  42%                  25%
First IV Antihypertensive




                              Metoprolol (n=277)          40%                  37%              23%


                            Nitroglycerin (n=241)         41%              27%               32%


                             Hydralazine (n=235)          41%                    45%               14%


                            Nicardapine (n=121)             51%                  28%            21%


    Sodium nitroprusside (n=82)                     22%            32%                   46%

                                                                  Percent of Patients


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




                   Katz et al. Am Heart J 2009;158:599-606.
  Blood Pressure Dynamics
• MAP = DBP + ([SBP - DBP]/3)

• MAP = (CO x SVR) + CVP
  – CO = HR x SV
Reference: Peacock et al.
                            Peacock et al. Critical Care 2011 [epub ahead of print].
                             CLUE Study
Evaluation of Intravenous niCardipine and Labetalol Use in the Emergency
                              Department




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



         Final multivariable logistic regression model†* for
              “met target SBP within first 30 minutes”




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




        Rhoney and Peacock. Am J Health-Syst Pharm. 2009; 66:1343-52.
  How Low Should You Go?
• Simple answer
  – 25% reduction in MAP within 1st hour
  – Target ~ 160/100 mm Hg by 2-6 hours




                            Marik and Varon. Critical Care 2003, 7:374-84.
  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
AHA/ASA Recommendations for
   BP Management in AIS




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




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




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




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




                Aiyagari and Gorelick. Stroke 2009;40:2251-56.
Sandset et al. Lancet 2011 [epub ahead of print].
Sandset et al. Lancet 2011 [epub ahead of print].
Sandset et al. Lancet 2011 [epub ahead of print].
Impact of Early Reduction




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




        Rhoney et al. Presented at the 2011 Neuro-Critical Care Society Meeting.
Guideline: SBP < 180 mm Hg
Intensive: SBP < 140 mm Hg
                             Anderson et al. Stroke 2010;41:307-12.
But No Direct Clinical Benefit
        at 90 Days…




                   Anderson et al. Lancet Neurol 2008;7:391–9.
Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) investigators Crit Care Med 2010;38:637-48.
Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) investigators Crit Care Med 2010;38:637-48.
Hematoma Expansion   Modified Rankin Scale Score




                       Qureshi et al. Arch Neurol. 2010;67:570-6.
Qureshi et al. Arch Neurol. 2010;67:570-6.
BP Goal by 1 hr: 11% vs. 56% (p=0.02)


                                        Liu-DeRyke et al. Neurocrit Care 2008;9:167-76.
n=51   n=20             n=51              n=20


              Stead et al. Neurology 2006;66:1878–81.
AHA/ACC Recommendations for
 BP Management in Acute HF




                Hunt et al. Circulation. 2009;119(14):e391-479.
What About the Rest?




          Kessler and Joudeh. Am Fam Physician. 2010;81:470-76.
Pitts and Adams. Ann Emerg Med 1998;31:214-8.
Grassi et al. J Clin Hypertens 2008;10:662–7.
BP Response to Rest




             Grassi et al. J Clin Hypertens 2008;10:662–7.
    Retrospective Cohort Study
                                                                 Untreated Treated
                                                                   n = 581        n = 435      p-value
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)      1 (0.2)       0.837
Death within 1 year, n (%)                                           9 (1.6)      9 (2.1)       0.534
            Levy et al. Accepted for poster presentation at ACEP Scientific Assembly 2011 (San Francisco, CA).
               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

								
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