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A n update in the management of Hypertensive Emergency In Patients with Acute Heart Failure

A n update in the management of Hypertensive Emergency In Patients with Acute Heart Failure. Yerizal Karani. Acute Heart failure. Acute Heart Failure. ESC Guideline. For diagnosis and treatment of Acute and chronic HF. 2008. Major Drugs for the Treatment of Acute Heart Failure.

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A n update in the management of Hypertensive Emergency In Patients with Acute Heart Failure

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  1. An update in the management of Hypertensive Emergency In Patients with Acute Heart Failure Yerizal Karani

  2. Acute Heart failure

  3. Acute Heart Failure ESC Guideline. For diagnosis and treatment of Acute and chronic HF. 2008

  4. Major Drugs for the Treatment of Acute Heart Failure

  5. Hypertensive Emergency

  6. Definitions • A hypertensive emergency is a situation that requires immediate reduction in blood pressure (BP) with parenteral agents because of acute or progressing target organ damage. • A hypertensive urgency is a situation with markedly elevated BP but without severe symptoms or progressive target organ damage, wherein the BP should be reduced within hours, often with oral agents. Kaplan, 2002

  7. Hypertensive Crises Hypertensive Urgency Hypertensive Emergency Markedly elevated BP Without severe symptoms or progressive target organ damage BP should be reduced within hours Oral agents Markedly elevated BP With acute or progressing target organ damage BP should be reduced immediate Parenteral agents Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9th Ed, Lippincott Williams & Wilkins 2006:609-630

  8. HTN Crisis Definitions • Severe (stage 2) acute elevation of BP SBP ≤ 160 mmHg DBP ≤ 100 mmHg • Hypertensive Urgency No evidence of organ failure BP reduction over several hours to days Oral treatment adequate

  9. HTN Crisis Definitions • Hypertensive emergency Severely elevated BP (>180/120mmHg) Acute onset Evidence of target-organ damage BRAIN, HEART,KIDNEYS, RETINA

  10. HYPERTENSIVE EMERGENCY Accelerated-malignant hypertension with papilledema Cerebrovascular conditions Hypertensive brain infarction with severe hypertension Intracerebral hemorrhage Subarachnoid hemorrhage Head trauma Cardiac conditions Acute aortic dissection Acute left ventricular failure Acute or impending myocardial infarction After coronary bypass surgery Renal conditions Acute glomerulonephritis Renovascular hypertension Renal crises from collagen-vascular diseases Severe hypertension after kidney transplantation

  11. Hypertensive emergency (cont’d) Excess circulating catecholamines Pheochromocytoma crisis Food or drug interactions with monoamine oxidase inhibitors Sympathomimetic drug use (cocaine) Rebound hypertension after sudden cessation of antihypertensive drugs automatic hyperreflexia after spinal cord injury Eclampsia Surgical conditions Severe hypertension in patients requiring immediate surgey Postoperative hypertension Postoperative bleeding from vascular suture lines Severe body burns Severe epistaxis Thrombotic thrombocytopenic purpura

  12. Pathophysiology • circulating cathecolamines • Activation of the renin-angiotensin-aldosterone axis • Altered baroreceptor function

  13. Pathophysiology vascular resistance • Endothelial damage • Arteriolar fibrinoid necrosis • Loss of autoregulatory function • Target organ ischemia

  14. Management of Hypertensive emergency • General principle : • the goal is, inhibit the progression of organ damage • parenteral drugs must be used • balance the benefit and the organ perfusion, particularly brain, myocardium and kidney

  15. Therapeutic guidelines • do not lower BP more than 25% over the first 1 hour unless necessary to protect other organs • reduce the SBP of 160 mmHg, DBP of 100 mmHg, or MAP of 120 mmHg, in the first 24 hours • begin the concomitant long-term therapy soon after the initial emergency treatment • attempt the established normotension within e few days

  16. Parenteral Drugs for Treatment of Hypertensive Emergencies based on JNC 7 Chobanian AV et al, The JNC 7 report, JAMA 2003;389-2560-70

  17. Parenteral Drugs for Treatment of Hypertensive Emergencies based on CHEST 2007 Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62

  18. Nitroglycerin Nitroglycerin is a potent venodilator and only at high doses affect arterial tone. It reduces BP by reducing cardiac ouput and preload which are undesirable effects in patient with compromised cerebral and renal perfusion Nifedipine Nifedipine has been widely used via oral or sublingual administration in the management of hypertensive emergencies. This mode of administration has not been approved by FDA and since JNC VI because it may cause sudden uncontrolled and severe reductions in blood pressure may precipitate cerebral, renal, and myocardial ischemia that have been associated with fatal outcomes

  19. Clonidine • Central alfa blocker, sedative effect • CI : in patient with Cerebrovascular accident • Rebound effect

  20. USE OF NICARDIPINE • Nicardipine : • . Dihydropiridine class of CCB • Reduce peripheral resistance --- blood pressure • water soluble, light insensitive, -- can be parenteraly used (deference with nifedipine / sodium nitroprusid)

  21. Calcium Channel Blocker Mechanism Ca++ Ca++ Blocking effect of CCB    Ca++plus Calmodulin Ca++plus Calmodulin    Myosin Kinase Myosin Kinase          Actin-Myosin Interaction Contraction   Ca++ Ca++

  22. NICARDIPINE CHARACTERISTIC 1.VASOSELECTIVITY Nicardipine selectivity 30.000 x in smooth muscle cells blood vessels compared with myocardium 2. Myocardial depression (-) 3. Negative inotropic (-) 4. Rapid and stable antihypertensive effects, reduce blood pressure gradually < 25% in 2 hours, minimal effects to heart rate 5. Increase blood flow in major organ : Renal, coroner, cerebral

  23. Mean blood pressure 103  11 mmHg Vertebral artery blood flow 183  65 mL/min Renal artery blood flow 563  29mL/min Coronary artery blood flow 121  42 mL/min Actions to increase organ blood flow Pharmacodynamic action Perdipine: 3 g/kg/min  20 min ⊿%) (Hypertensive patients, n = 9) Mean blood pressure Vertebral artery blood flow Renal blood flow Coronary blood flow 60 Blood flow change rate Baseline value 40 20 0 Mean blood pressure change rate -10 -20 (⊿%) (Shoji Suzuki, et al., The 20th Annual Scientific Meeting of the Japanese Society of Hypertension: 1997)

  24. Tissue selectivity betweenCalcium Antagonist Bristow et al. Br J Pharmacol1984; 309:82

  25. Comparison between Calcium Antagonist Kerins DM. Goodman Gilman’s.10th ed.2001:843-70

  26. Perdipine Injection - Clinical data for Acute Heart Failure -

  27. Comparison Study with Placebo in Patients with AHF • Subjects: • Patients with acute heart failure with CI  2.5 L/min/m2, • PCWP  15 mmHg, and SBP  100 mmHg (n=81) • Design: • Multicenter, randomized, placebo-controlled, double-blind • comparative study • Treatment: • Enrolled patients were randomly allocated to receive either • 1) Intravenous infusion of nicardipine 1 g/kg/min for 1 hour • or • 2) Intravenous infusion of placebo for 1 hour [Kumada T. et al. Jpn. Pharmacol. Ther. 23:375, 1995]

  28. (mmHg) Nicardipine (n=28) 200 175 Placebo (n=28) 150 NS NS NS 125 ** ** ** 100 NS NS NS 75 ** ** ** 50 (min) Baseline 15 30 60 Changes in Arterial Pressure Following IV-Infusion of Nicardipine and Placebo *: p<0.05 **: p<0.01 (vs baseline) [Kumada T. et al. Jpn. Pharmacol. Ther. 23:375, 1995]

  29. (L/min/m2) 5 Nicardipine (n=28) 4 Placebo (n=28) 3 ** ** ** 2 NS NS NS 1 0 (min) Baseline 15 30 60 Changes in Cardiac Index (CI) Following IV-Infusion of Nicardipine and Placebo *: p<0.05 **: p<0.01 (vs baseline) [Kumada T. et al. Jpn. Pharmacol. Ther. 23:375, 1995]

  30. (mmHg) Nicardipine (n=20) 40 Placebo (n=19) 30 NS NS NS 20 * * ** 10 0 Baseline 15 30 60 (min) Changes in Pulmonary Capillary Wedge Pressure (PCWP) Following IV-Infusion of Nicardipine and Placebo *: p<0.05 **: p<0.01 (vs baseline) [Kumada T. et al. Jpn. Pharmacol. Ther. 23:375, 1995]

  31. Nicardipine (n=28) (dyne･sec/cm5) 3000 Placebo (n=29) NS NS NS 2000 ** ** ** 1000 0 Baseline 15 30 60 (min) Changes in Pulmonary Vascular Resistance (PVR) Following IV-Infusion of Nicardipine and Placebo *: p<0.05 **: p<0.01 (vs baseline) [Kumada T. et al. Jpn. Pharmacol. Ther. 23:375, 1995]

  32. Nicardipine (n=20) Placebo (n=19) Changes in Pulmonary Capillary Wedge Pressure (PCWP) and Cardiac Index (CI) (L/min/m2) 3.4 60 min 3.0 Cardiac Index (CI) 30 min 2.6 15 min (Mean±SD) Baseline Baseline 2.2 15 min 1.8 60 min 30 min 0 14 18 22 26 30 34 38 （mmHg） Pulmonary Capillary Wedge Pressure (PCWP) [Kumada T. et al. Jpn. Pharmacol. Ther. 23:375, 1995]

  33. Comparison Study with Intravenous Diltiazem Subjects: Patients requiring a rapid reduction in BP (DBP  115 mmHg) Design: Multicenter, randomized, single-blind comparative study Dosage Nicardipine: Started at 0.5 g/kg/min  Increased up to 10 g/kg/min if necessary Diltiazem: Started at 5 g/kg/min  Increased up to 15 g/kg/min if necessary Duration of drug administration Dose titration: 1 hour Maintenance infusion: 24 hours Yoshinaga K. et al. Igaku no Ayumi 1993: 165:437

  34. Stability of antihypertensive effect better than Diltiazem Yoshinaga K. et al. Igaku no Ayumi 1993: 165:437

  35. Nicardipine vs Nitrovasodilators Pepine CJ. Intravenous nicardipine: cardiovascular effects and clinical relevance. Clin Ther. 1988;10:316-25.

  36. Dosage and Administration Start with the lowest dose. Eg 0.5 mcg/BW/min  15 drops  monitoring, if in 5-15 minutes there’s no significant blood pressure reducing  Increasing drip until 20 drop , and then can be increased until desirable blood pressure achieved ( about 3-5 drops each after monitoring) Monitoring blood pressure and heart rate frequently Before choose to switch to oral, 1 hour before Perdipine is stopped, give oral drugs and Perdipine is tappered of

  37. TAKE HOME MESSAGES • Hypertensive Crises: urgent situation need rapid management to prevent organ damage • Antihypertensive agent: should be fast action parenteral titratable

  38. TAKE HOME MESSAGES • Nicardipine(Perdipine ®): Calcium Antagonist recommended by JNC 7, AHA, 2007, CHEST 2007 to manage hypertensive emergency • Nicardipine(Perdipine ®): has favorable antiischemic increase myocardial oxygen supply increase cardiac index  in patients with acute heart failure

  39. THANK YOU FOR YOUR ATTENTION TAKE CARE OF YOUR HEART

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