Dr Nahed Sherbini ,Consultant Internist ,Head of Internal Medicine Department
2010 KFH, Medina
   ED
   Medical & Surgical Wards
   MICU
   SICU
   OR



    Varon J, Fromm RE. Postgrad Med. 1996;99:189-203.
   Hypertensive Emergencies

   Hypertensive Urgencies

   An Approach to Drug Treatment of HU and HE
   Affects at least 1 BILLION individuals
    worldwide.

   Most current (2003) evidence basis for
    chronic management— (JNC 7)—lacks
    guidance for acute management of patients
    presenting with severe acute elevations of BP.

         JNC 7, JAMA 2003; 289:2560-2572.
   Data are largely lacking.

   In a single-center Italian study, HU or HE

     HU:HE ratio of 3:1 in that study




         Zampaglione et al, Hypertension 1996;27:144.
   Hypertensive emergencies and urgencies
     Account for 3% of all ED visits1


   An “Internal Medicine” ED
     N=14,209
     1634 had a medical urgency or emergency2
      ▪ 27.4% of these were hypertensive crises


       1.   Kitiyakara C, Guzman N. J Am Soc Nephrol. 1998;9:133-142.
       2.   Zampaglione B, et al. Hypertension. 1996;27:144-147.
JNC7


BP Classification      SBP mmHg         DBP mmHg
Normal                 <120       and   <80
Prehypertension        120–139    or    80–89

Stage 1 Hypertension   140–159    or    90–99

Stage 2 Hypertension   >160       or    >100
   Stage 3 hypertension (JNC 6):
     Systolic > 180, Diastolic > 110
     Functionally, this is “hypertensive urgency”


   What about “crisis,” “emergency,” and
    “urgency”?


          JNC 7, JAMA 2003; 289:2560-2572.
   “hypertensive crisis” is an acute, severe, stage
    2 or 3 elevation BP.


   Crisis is then differentiated into hypertensive
    “emergencies” &“urgencies”.


         JNC 7, JAMA 2003; 289:2560-2572.
Hypertensive           Severe elevation in BP
emergency              (>180/120 mmHg)                                         Hypertensive Crisis
                       complicated by evidence of
                       impending or progressive
                       target organ dysfunction


                                                                Hypertensive      Hypertensive        Perioperative
Hypertensive           Severe elevation in BP                     urgency          emergency          hypertension
urgency                without progressive
                       target organ dysfunction




                                                              Emergency          Intensive care      Operating room
                                                              department              unit           post-anesthesia
                                                                                                           care




               Chobanian AV et al. Hypertension. 2003;42:1206-1252.
Brain
  Hypertensive encephalopathy                        Retina
  Stroke                                             Hemorrhages
                                                     Exudates
                                                     Papilledema

Cardiovascular System
Unstable angina
Acute heart failure
Acute myocardial infarction                         Kidney
Acute aortic dissection                             Hematuria
Dissecting aortic aneurysm                          Proteinuria
                                                    Decreasing renal function



                                Adapted from Varon J, Marik PE. Chest. 2000;118:214-227.
   Essential hypertension
     Medication noncompliance

   Secondary hypertension
       Aortic coarctation
       Cushing’s syndrome
       Elevated ICP
       Renal dysfunction
       Pregnancy
       Hyperparathyroidism
       Hyperthyroidism
       Pheochromocytoma
       Primary aldosteronism

            JNC 7, JAMA 2003; 289:2560-2572.
   Medical                                         ● Surgical
                                                      – Cardiac surgery
     Uncontrolled HTN
                                                      – Major vascular surgery
        ▪ Noncompliance
                                                        - Carotid endarterectomy
     Drug-induced HTN
                                                        - Aortic surgery
        ▪ Cocaine,
                                                      – Neurosurgery
          amphetamines
                                                      – Head and neck surgery
        ▪ Drug withdrawal
                                                      – Renal transplantation
        ▪ Drug-drug interactions
                                                      – Major trauma – burns or head
     Endocrine disorders                               injury


Varon J, Fromm RE. Postgrad Med. 1996;99:189-203.
• Oral contraceptives

• Steroids

• NSAIDs

• Nasal decongestants

• Appetite suppressants
   Hypertensive                                             Hypertensive
    Urgencies                                                 Emergencies
                                                               Chest pain
       Arrhythmia                                             Dyspnea
       Epistaxis                                              Neurologic deficits
       Headache
       Psychomotor agitation                                Usual Primary ED
                                                              Diagnosis
                                                               CVA
                                                               Acute pulmonary edema
   Usual Primary ED                                           Hypertensive
    Diagnosis                                                   encephalopathy
     Hypertension                                             Acute heart failure

           Zampaglione et al, Hypertension 1996;27:144.
Four Categories of Presentation
1. Mild, uncomplicated
2. Transient
3. Emergencies
4. Urgencies
   Mild, Uncomplicated HTN
     Diastolic BP <115 mmHg without end organ
      symptoms
     Educate, do not treat, arrange follow up

   Transient HTN
     A reaction to some condition
      ▪ Pain, fright, epistaxis,
        drug OD
     Treat the condition
Average Percent Reduction
Stroke incidence                35–40%

Myocardial infarction           20–25%

Heart failure                     50%
   Goal in hypertensive urgency is to reduce
    MAP (MAP= ( 2 Diastolic + systolic) / 3) by
    10-15% and/or to a DBP of 110 . . . within
    hours.

   HU can generally be managed with oral
    medications and requires BP lowering over
    24-48 h.

         JNC 7, JAMA 2003; 289:2560-2572.
Lifestyle Modifications


                                 Not at Goal Blood Pressure (<140/90 mmHg)
                       (<130/80 mmHg for those with diabetes or chronic kidney disease)


                                               Initial Drug Choices


                           Without Compelling                                                With Compelling
                               Indications                                                      Indications


     Stage 1 Hypertension                     Stage 2 Hypertension                      Drug(s) for the compelling
(SBP 140–159 or DBP 90–99 mmHg)           (SBP >160 or DBP >100 mmHg)                          indications
  Thiazide-type diuretics for most.      2-drug combination for most (usually            Other antihypertensive drugs
 May consider ACEI, ARB, BB, CCB,             thiazide-type diuretic and               (diuretics, ACEI, ARB, BB, CCB)
          or combination.                   ACEI, or ARB, or BB, or CCB)                           as needed.


                                                    Not at Goal
                                                  Blood Pressure

                                    Optimize dosages or add additional drugs
                                       until goal blood pressure is achieved.
                                 Consider consultation with hypertension specialist.
Compelling Indication   Initial Therapy Options   Clinical Trial Basis

                                                  ACC/AHA Heart Failure
Heart failure           THIAZ, BB, ACEI, ARB,     Guideline, MERIT-HF,
                        ALDO ANT                  COERNICUS, RALES


Post MI                                           ACC/AHA Post-MI
                        BB, ACEI, ALDO ANT        Guideline, BHAT,
                                                  SAVE, Capricorn,
                                                  ALLHAT, HOPE,
                                                  ANBP2, LIFE,
High CAD risk           THIAZ, BB, ACE, CCB       CONVINCE
Compelling Indication   Initial Therapy Options   Clinical Trial Basis
Diabetes               THIAZ, BB, ACE, ARB, C NKF-ADA
                       CB                     Guideline, UKPDS, AL
                                              LHAT
Chronic kidney disease ACEI, ARB
                                              NKF Guideline,
                                              Captopril Trial,
                                              RENAAL, IDNT, REIN,
                                              AASK
Recurrent stroke       THIAZ, ACEI
prevention                                    PROGRESS
   Reduce MAP by ≤ 25% during the 1st minutes
    to 1 h.
   If stable, reduce BP to 160/100-110 mmHg in
    next 2-6 h.
   Conditions requiring special management
     Aortic dissection
   Stroke eligible for thrombolytic agents
   Ischemic stroke


                           Chobanian AV et al. Hypertension. 2003;42:1206-1252.
Patients with chronic hypertension
Cerebral Blood Flow                                      autoregulate cerebral blood flow
                                                             around higher set points

                                                           Patients with cerebral ischemia
 Increasing risk of                                       lose their ability to autoregulate
   hypertensive                                                                       Ischemia
  encephalopathy                       Normotensive

                                                                              Chronic hypertensive
  Increasing risk
    of ischemia


                                 0            50           100           150          200      250
                                                        MAP (mm Hg)


                    Adapted with permission from Varon J, Marik PE. Chest. 2000;118:214-227.
NORMAL AUTOREGULATION        AUTOREGULATION FAILURE


       RISE IN BP                 RISE IN BP




     ARTERIAL AND              FAILURE OF
     ARTERIOLAR                VASOCONSTRICTION
     CONSTRICTION




    Normal flow.(flow=P/r)      ENDOTHELIAL DAMAGE
                                (due to shear stress on the wall)
   Patients with marked BP elevations and acute
    target-organ damage

     Admitted to an ICU for continuous monitoring of BP.


     Should receive parenteral antihypertensive therapy with
         an agent appropriate for the individual patient.




The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
                                          Blood Pressure. US Dept of HHS; NIH publication No. 04-5230; 2004:54.
Ref : CHEST 2007 ; 131 : 1949-1962 : Hypertensive crises : challenges and management
Ref : CHEST 2007 ; 131 : 1949-1962 : Hypertensive crises : challenges and management
47-Year-Old
Complains Of Chest Pain
        BP 162/110
   NTG
     Relieves only chest pain
     No mortality difference in 77,000 patients

    -blockers
   Antiplatelets: ASA, clopidogrel
   Anticoagulants: LMWH, UFH
   GP IIb/IIIa antagonist or DTI w/clopidogrel

                                             2007 AHA/ACC Guidelines
Drug                                       Nitroprusside   Nitroglycerin
Rapid onset of peak effect                                         ++++            +++
Afterload reduction                                                ++++             +
Preload reduction                                                   ++             ++++
Coronary steal reported                                              +               0

Coronary dilation – large vessel                                     +             ++++

Coronary dilation – small vessel                                    +/-             +/-

Tachycardia                                                         ++              ++
Potential for symptomatic hypotension                               ++             +++

Ease of administration                                              ++             +++
Cyanide toxicity                                                   ++++              0




                      Pepine CJ. Clin Ther. 1988;10:316-325.
   Must decrease shear forces
     Do not use inotropics



   Esmolol
   Labetolol



                    Tintinalli, 4th ed.
Esmolol                                Labetalol
                                                  -Blocker                            - and -Blocker
Administration                                   Bolus                                   Bolus
                                          Continuous infusion                     Continuous infusion
Onset                                           Rapid (60 s)2              Intermediate (peak 5-15 min)2
Offset (Duration of action)                Rapid (10-20 min)2                         Slower (2-4 h)2

HR                                               Decreased                                     +/-
SVR                                                     0                                Decreased
Cardiac output                                   Decreased                                     +/-
Myocardial O2 balance                              Positive                                Positive
Contraindications                          Sinus bradycardia                      Severe bradycardia
                                            Heart block >1°                         Heart block >1°
                                           Overt heart failure                    Overt heart failure
                                           Cardiogenic shock                      Cardiogenic shock

         1. Hoffman BB. In: Hardman JG, Limbird LE, eds. Goodman and Gilman’s Pharmacological Basis of
            Therapeutics. 10th ed. New York, NY: McGraw-Hill; 1997:215-268.
         2. Varon J, Malik PE. Chest. 2000;118:214-227.
Nicardipine                       Diltiazem                       Verapamil
                 (dihydropyridine)              (benzothiazepine)               (phenylalkylamine)
 Peripheral
Vasodilation1
                       +++++                             +++                              +++
  Coronary
Vasodilation2
                       +++++                             +++                             ++++
Suppression
of SA Node2                +                           +++++                            +++++
Suppression
of AV Node2                0                            ++++                            +++++
Suppression
 of Cardiac                0                              ++                             ++++
Contractility2



                                                Frishman WH, et al. Med Clin North Am. 1988;72:523-547. .1
                 Adapted from Goodman and Gilman’s: The Pharmacologic Basis of Therapeutics. 9th ed. 2001. .2
All Patients Treated with Drug
1,400,000

             1,200,444
1,200,000                   1,133,717
                                                                        2004        2005         2006

1,000,000


 800,000                                 735,647


 600,000
                                                      502,518

 400,000
                                                                    312,432
                                                                               240,785

 200,000                                                                                   139,104
                                                                                                         8,288
       0
            Nitroglycerin   Labetalol   Hydralazine   Enalaprilat   Esmolol     SNP      Nicardipine   Fenoldopam

                                        Thomson Patient Level Data. 2006
 HTN is extremely prevalent &
 hypertensive crises will become
 increasingly common in the ED.
So, What is new?
http://www.nhlbi.nih.gov/guidelines/hypertension/jnc8/index.htm
   The Eighth Report of the Joint National
    Committee on
    Prevention, Detection, Evaluation, and
    Treatment of High Blood Pressure (JNC 8)

   Update of the JNC 7 Report
   Expected Availability for Public Review and
    Comment: Spring 2011
   Expected Release Date: Fall 2011
Thank you for your attention

Hypertensive Emergencies

  • 2.
    Dr Nahed Sherbini,Consultant Internist ,Head of Internal Medicine Department 2010 KFH, Medina
  • 3.
    ED  Medical & Surgical Wards  MICU  SICU  OR Varon J, Fromm RE. Postgrad Med. 1996;99:189-203.
  • 4.
    Hypertensive Emergencies  Hypertensive Urgencies  An Approach to Drug Treatment of HU and HE
  • 6.
    Affects at least 1 BILLION individuals worldwide.  Most current (2003) evidence basis for chronic management— (JNC 7)—lacks guidance for acute management of patients presenting with severe acute elevations of BP. JNC 7, JAMA 2003; 289:2560-2572.
  • 7.
    Data are largely lacking.  In a single-center Italian study, HU or HE  HU:HE ratio of 3:1 in that study Zampaglione et al, Hypertension 1996;27:144.
  • 8.
    Hypertensive emergencies and urgencies  Account for 3% of all ED visits1  An “Internal Medicine” ED  N=14,209  1634 had a medical urgency or emergency2 ▪ 27.4% of these were hypertensive crises 1. Kitiyakara C, Guzman N. J Am Soc Nephrol. 1998;9:133-142. 2. Zampaglione B, et al. Hypertension. 1996;27:144-147.
  • 10.
    JNC7 BP Classification SBP mmHg DBP mmHg Normal <120 and <80 Prehypertension 120–139 or 80–89 Stage 1 Hypertension 140–159 or 90–99 Stage 2 Hypertension >160 or >100
  • 11.
    Stage 3 hypertension (JNC 6):  Systolic > 180, Diastolic > 110  Functionally, this is “hypertensive urgency”  What about “crisis,” “emergency,” and “urgency”? JNC 7, JAMA 2003; 289:2560-2572.
  • 12.
    “hypertensive crisis” is an acute, severe, stage 2 or 3 elevation BP.  Crisis is then differentiated into hypertensive “emergencies” &“urgencies”. JNC 7, JAMA 2003; 289:2560-2572.
  • 13.
    Hypertensive Severe elevation in BP emergency (>180/120 mmHg) Hypertensive Crisis complicated by evidence of impending or progressive target organ dysfunction Hypertensive Hypertensive Perioperative Hypertensive Severe elevation in BP urgency emergency hypertension urgency without progressive target organ dysfunction Emergency Intensive care Operating room department unit post-anesthesia care Chobanian AV et al. Hypertension. 2003;42:1206-1252.
  • 14.
    Brain Hypertensiveencephalopathy Retina Stroke Hemorrhages Exudates Papilledema Cardiovascular System Unstable angina Acute heart failure Acute myocardial infarction Kidney Acute aortic dissection Hematuria Dissecting aortic aneurysm Proteinuria Decreasing renal function Adapted from Varon J, Marik PE. Chest. 2000;118:214-227.
  • 15.
    Essential hypertension  Medication noncompliance  Secondary hypertension  Aortic coarctation  Cushing’s syndrome  Elevated ICP  Renal dysfunction  Pregnancy  Hyperparathyroidism  Hyperthyroidism  Pheochromocytoma  Primary aldosteronism JNC 7, JAMA 2003; 289:2560-2572.
  • 16.
    Medical ● Surgical – Cardiac surgery  Uncontrolled HTN – Major vascular surgery ▪ Noncompliance - Carotid endarterectomy  Drug-induced HTN - Aortic surgery ▪ Cocaine, – Neurosurgery amphetamines – Head and neck surgery ▪ Drug withdrawal – Renal transplantation ▪ Drug-drug interactions – Major trauma – burns or head  Endocrine disorders injury Varon J, Fromm RE. Postgrad Med. 1996;99:189-203.
  • 17.
    • Oral contraceptives •Steroids • NSAIDs • Nasal decongestants • Appetite suppressants
  • 18.
    Hypertensive  Hypertensive Urgencies Emergencies  Chest pain  Arrhythmia  Dyspnea  Epistaxis  Neurologic deficits  Headache  Psychomotor agitation  Usual Primary ED Diagnosis  CVA  Acute pulmonary edema  Usual Primary ED  Hypertensive Diagnosis encephalopathy  Hypertension  Acute heart failure Zampaglione et al, Hypertension 1996;27:144.
  • 19.
    Four Categories ofPresentation 1. Mild, uncomplicated 2. Transient 3. Emergencies 4. Urgencies
  • 20.
    Mild, Uncomplicated HTN  Diastolic BP <115 mmHg without end organ symptoms  Educate, do not treat, arrange follow up  Transient HTN  A reaction to some condition ▪ Pain, fright, epistaxis, drug OD  Treat the condition
  • 22.
    Average Percent Reduction Strokeincidence 35–40% Myocardial infarction 20–25% Heart failure 50%
  • 24.
    Goal in hypertensive urgency is to reduce MAP (MAP= ( 2 Diastolic + systolic) / 3) by 10-15% and/or to a DBP of 110 . . . within hours.  HU can generally be managed with oral medications and requires BP lowering over 24-48 h. JNC 7, JAMA 2003; 289:2560-2572.
  • 25.
    Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Without Compelling With Compelling Indications Indications Stage 1 Hypertension Stage 2 Hypertension Drug(s) for the compelling (SBP 140–159 or DBP 90–99 mmHg) (SBP >160 or DBP >100 mmHg) indications Thiazide-type diuretics for most. 2-drug combination for most (usually Other antihypertensive drugs May consider ACEI, ARB, BB, CCB, thiazide-type diuretic and (diuretics, ACEI, ARB, BB, CCB) or combination. ACEI, or ARB, or BB, or CCB) as needed. Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.
  • 26.
    Compelling Indication Initial Therapy Options Clinical Trial Basis ACC/AHA Heart Failure Heart failure THIAZ, BB, ACEI, ARB, Guideline, MERIT-HF, ALDO ANT COERNICUS, RALES Post MI ACC/AHA Post-MI BB, ACEI, ALDO ANT Guideline, BHAT, SAVE, Capricorn, ALLHAT, HOPE, ANBP2, LIFE, High CAD risk THIAZ, BB, ACE, CCB CONVINCE
  • 27.
    Compelling Indication Initial Therapy Options Clinical Trial Basis Diabetes THIAZ, BB, ACE, ARB, C NKF-ADA CB Guideline, UKPDS, AL LHAT Chronic kidney disease ACEI, ARB NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK Recurrent stroke THIAZ, ACEI prevention PROGRESS
  • 28.
    Reduce MAP by ≤ 25% during the 1st minutes to 1 h.  If stable, reduce BP to 160/100-110 mmHg in next 2-6 h.  Conditions requiring special management  Aortic dissection  Stroke eligible for thrombolytic agents  Ischemic stroke Chobanian AV et al. Hypertension. 2003;42:1206-1252.
  • 29.
    Patients with chronichypertension Cerebral Blood Flow autoregulate cerebral blood flow around higher set points Patients with cerebral ischemia Increasing risk of lose their ability to autoregulate hypertensive Ischemia encephalopathy Normotensive Chronic hypertensive Increasing risk of ischemia 0 50 100 150 200 250 MAP (mm Hg) Adapted with permission from Varon J, Marik PE. Chest. 2000;118:214-227.
  • 30.
    NORMAL AUTOREGULATION AUTOREGULATION FAILURE RISE IN BP RISE IN BP ARTERIAL AND FAILURE OF ARTERIOLAR VASOCONSTRICTION CONSTRICTION Normal flow.(flow=P/r) ENDOTHELIAL DAMAGE (due to shear stress on the wall)
  • 31.
    Patients with marked BP elevations and acute target-organ damage  Admitted to an ICU for continuous monitoring of BP.  Should receive parenteral antihypertensive therapy with an agent appropriate for the individual patient. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. US Dept of HHS; NIH publication No. 04-5230; 2004:54.
  • 32.
    Ref : CHEST2007 ; 131 : 1949-1962 : Hypertensive crises : challenges and management
  • 33.
    Ref : CHEST2007 ; 131 : 1949-1962 : Hypertensive crises : challenges and management
  • 34.
  • 35.
    NTG  Relieves only chest pain  No mortality difference in 77,000 patients  -blockers  Antiplatelets: ASA, clopidogrel  Anticoagulants: LMWH, UFH  GP IIb/IIIa antagonist or DTI w/clopidogrel 2007 AHA/ACC Guidelines
  • 36.
    Drug Nitroprusside Nitroglycerin Rapid onset of peak effect ++++ +++ Afterload reduction ++++ + Preload reduction ++ ++++ Coronary steal reported + 0 Coronary dilation – large vessel + ++++ Coronary dilation – small vessel +/- +/- Tachycardia ++ ++ Potential for symptomatic hypotension ++ +++ Ease of administration ++ +++ Cyanide toxicity ++++ 0 Pepine CJ. Clin Ther. 1988;10:316-325.
  • 38.
    Must decrease shear forces  Do not use inotropics  Esmolol  Labetolol Tintinalli, 4th ed.
  • 39.
    Esmolol Labetalol -Blocker - and -Blocker Administration Bolus Bolus Continuous infusion Continuous infusion Onset Rapid (60 s)2 Intermediate (peak 5-15 min)2 Offset (Duration of action) Rapid (10-20 min)2 Slower (2-4 h)2 HR Decreased +/- SVR 0 Decreased Cardiac output Decreased +/- Myocardial O2 balance Positive Positive Contraindications Sinus bradycardia Severe bradycardia Heart block >1° Heart block >1° Overt heart failure Overt heart failure Cardiogenic shock Cardiogenic shock 1. Hoffman BB. In: Hardman JG, Limbird LE, eds. Goodman and Gilman’s Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill; 1997:215-268. 2. Varon J, Malik PE. Chest. 2000;118:214-227.
  • 40.
    Nicardipine Diltiazem Verapamil (dihydropyridine) (benzothiazepine) (phenylalkylamine) Peripheral Vasodilation1 +++++ +++ +++ Coronary Vasodilation2 +++++ +++ ++++ Suppression of SA Node2 + +++++ +++++ Suppression of AV Node2 0 ++++ +++++ Suppression of Cardiac 0 ++ ++++ Contractility2 Frishman WH, et al. Med Clin North Am. 1988;72:523-547. .1 Adapted from Goodman and Gilman’s: The Pharmacologic Basis of Therapeutics. 9th ed. 2001. .2
  • 41.
    All Patients Treatedwith Drug 1,400,000 1,200,444 1,200,000 1,133,717 2004 2005 2006 1,000,000 800,000 735,647 600,000 502,518 400,000 312,432 240,785 200,000 139,104 8,288 0 Nitroglycerin Labetalol Hydralazine Enalaprilat Esmolol SNP Nicardipine Fenoldopam Thomson Patient Level Data. 2006
  • 42.
     HTN isextremely prevalent & hypertensive crises will become increasingly common in the ED.
  • 43.
  • 44.
  • 45.
    The Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8)  Update of the JNC 7 Report  Expected Availability for Public Review and Comment: Spring 2011  Expected Release Date: Fall 2011
  • 46.
    Thank you foryour attention