國軍高雄總醫院 心臟血管外科 趙家聲醫師

1. Hypertensive Crises 國軍高雄總醫院 心臟血管外科 趙家聲醫師

2. Franklin D. Roosevelt, 32nd president of the United States • His Death on April 12, 1945 • Steve Early, press secretary for the White House, stated officially that "the President was given a thorough examination by seven or eight physicians, including some of the most eminent in the country, and was pronounced organically sound in every way."

3. Headlines of the StLouis Post-Dispatch, April 13, 1945 Messerli F. N Engl J Med 1995;332:1038-1039

4. Diastolic and Systolic Arterial Pressure of Franklin D Messerli F. N Engl J Med 1995;332:1038-1039

5. Although only a small spot in the large panorama of hypertension, hypertensive crises represent, on one hand, the most immediate danger to those afflicted and, on the other, the most dramatic proof of the life-saving potential of anti-hypertensive therapy. ---Norman M. Kaplan

6. Why is high blood pressure associated with a greater rate of cardiovascular events? • The hemodynamic consequences of increased arterial-wall tension may explain certain events, such as hemorrhagic stroke, aortic dissection, and acute pulmonary edema. • other mechanisms must be invoked in linking elevated blood pressure with the premature development of atherosclerosis and an increased risk of acute vascular events. • increased sympathetic activity, • enhanced activity of the renin–angiotensin system, • environmental and psychosocial factors.

7. Panza J. N Engl J Med 2001;345:1337-1340

10. Fibrinoid necrosis

14. Pathophysiology Curves of CBF Breakthrough vasodilation

16. Parenteral Agents for Hypertensive Emergency 1.Rapid onset of action 2. IV administration 3. Titratable! 4. Vasodilator 5. Short half life

17. Anti-Hypertensive Drugs --- Diuretics (Furosemide) 64 patients with hypertensive encephalopathy and diastolic pressure >135 mmHg, 40mg iv furosemide alone 225/144→166/102 mmHg over 5 hours in 12 patients Remaining 52 patients still had a diastolic pressure higher than 125 mmHg 1 hour after medication. McNair A. Acta Med Scand 1986;220:15-23

18. Anti-Hypertensive Drugs Nitrates: Nitroglycerine; Nitroprusside Adrenergic Blockers: Labetalol; Esmolol Calcium Channel Blockers:Nicardipine

19. Nitroglycerine Mechanism : Dilate vein, artery and capillary Administration : IV infusion Onset : 30sec-1 min Duration : 2~10 min Advantage : 1. Increase coronary blood flow 2. Reduce myocardial O2 consumption Disadvantage : 1. Hypotension, unpredictable! 2. Reflex tachycardia 3. Headache, nausea, vomiting 4. Increase ICP

20. Nitroprusside Mechanism : Direct artery and vein dilation Administration : IV infusion Onset : Seconds Duration : Continuous, during infusion Advantage : Balanced  of preload & afterload Disadvantage : 1. Excessive hypotension 2. Reflex tachycardia 3. Light sensitivity 4. Potential -CN/-SCN toxicity 5. Potential coronary artery steal

21. Labetalol Mechanism :  and -1 blockade Administration : Bolus/infusion Onset : bolus -- 5~30 min infusion -- 15~60 min Duration : 2~6 hrs Advantage : 1. Little change in HR and C.O. 2. Intra-A or ICU monitoring (-) Disadvantage : 1. Orthostatic hypotension 2. Urinary retension 3. -blocker’s contra-indications

22. Mechanisms of Nicardipine ◆ Interfere Ca2+ influx ◆ Endothelin-1 antagonism ◆ Avoid [Ca2+]i accumulation ◆ Vasodilating & cellular protection

23. Vascular Selectivity of CCB Nicardipine對血管的選擇性最高 Ratio of IC-50 for vascular/cardiac tissue Frishman W.H. et al: J Clin Pharmacol, 29: 481-87, 1989

24. 血壓，心搏數的變化  維持穩定血壓,不會過度降低血壓

25. 投藥前收縮壓別效果 血壓愈高降壓效果愈顯著 (%) 0 20 40 60 80 100 ~159 mmHg 71.0 160~179 mmHg 80.8 180 mmHg ~ 87.3 顯著效果 有效

26. Comparison of Nicardipine with Nitroglycerin for Perioperative Hypertension  反射性心跳過快較為和緩 Source: ACTA ANAESTHESIOL SIN 33:199-204, 1995

27. Comparison of Nicardipine with Nitroglycerin for Perioperative Hypertension  易操控調節用量

28. Effect of Nicardipine During Cerebral Aneurysm Surgery  降壓時,不會減少腦部血流量 Anesth Analg 1993, 76:1227-33

29. Effects of Nicardipine in Coronary Artery Disease  有意義的增加CAD病患CO&CBF

30. 調配禁忌 • PDI 不可與5% Sodium Bicarbonate or Ringer’s solution 配用

31. Perdipine Injection Pharmacokinetics ◆ T1/2 : 50~63 minutes (healthy, 10~20 g/kg, iv; plasma conc.of unchanged NIC) 22~45 minutes (general anesthesia, 10~30 g/kg, iv) ◆ Plasma protein binding>90% without drug interaction with alcuronium, diazepam, pentazocine, propranolol, thiopental, tolbutamine, trichlormethiazide

32. Perdipine Injection Contraindications 1.Known hypersensitivity to the drug. 2. Incomplete hemostasis/intracranial hemorrhage.(?) 3. IICP at the acute cerebral stroke.(?)

33. A high rate of tolerability among patients with intracerebral hemorrhage who were treated with intravenous nicardipine using mean arterial pressure goals defined by American Heart association guidelines within 24 hrs of symptom onset. Crit Care Med 2006;34:1975-1980

34. Guidelines for the Early Management of Adults with Ischemic Stroke (AHA/ASA Guideline) ---Stroke. 2007;38:1655-1711.

35. Medical Therapy for Acute Aortic dissection • Medical treatment is started upon clinical suspicion! • “Anti-impulse” therapy --- reducing mean arterial pressure and myocardial contractility (dp/dt) • Labetalol (α1-adrenergic blockade with nonselective ß-blockade) • Nitroprusside alone will increase the dp/dt

36. Perdipine Injection Summary ◆No negative inotropic effect ◆ Increase CO & ejection fraction ◆ Increase coronary & cerebral blood flow ◆ Coronary steal (-) ◆ Anti-vasospasm effect

38. Thank you for your attention!