King Faisal Specialist Hospital and Research Center (2007-1428)

1. ICU Case Presentation King Faisal Specialist Hospital and Research Center (2007-1428) ManarLashkar Samah Al-shehri Pharm.D candidates Supervised by: Dr. MazenKadri

2. Hypertension affects > 65 million people in the United States and is one of the leading causes of death • One to two percent of patients with hypertension have acute elevations of BP that require urgent medical treatment 2 Manar & Samah

3. Hypertensive Crisis Degree of BP elevation Presence of end-organ damage 3 Manar & Samah

4. Outline Case Scenario Difference between hypertensive emergency and urgency Management of hypertensive crisis Special conditions of hypertensive crisis 4 Manar & Samah

5. 24 years old single female with a history of • Systemic Lupus Erythrematosus (SLE) • 8 years on steroid therapy • Lupus nephritis • Multiple viral warts • Leukopenia • End Stage Renal Disease (ESRD) • As complication of lupus nephritis • Hemodialysis (HD) 3 times a week for the past 6 months • Planned for renal transplant • Hypertension (HTN) • Not compliant to restricted Na intake • methyldopa stopped 2 months ago because of the SLE like side effect • BP was controlled on the medication Case Scenario 6 Manar & Samah

6. She was on • SLE: • Prednisolone 5 mg PO OD • ESRD: • Epoeitin 8000 units SC 3 times a week • Sevelamer 800 mg PO TID • One a 0.25 mcg PO OD • Multivitamin 1 tab PO OD • HTN: • Metoprolol 100 mg PO TID • Clonidine 200 mcg PO TID • Nifedipine LA 60 mg PO TID Case Scenario 7 Manar & Samah

7. Previous Investigations Ejection fraction = 55%(on 12/2007) ANA was positive (on 12/2007) Case Scenario 8 Manar & Samah

8. On 14/3/2008Came to the hospital ER with • Shortness of breath (orthopnea) for one day • Blood pressure 230/120 mmHg • Chest x-ray reveled pulmonary interstitial infiltration • No history of : • Cough • Palpitation • Chest pain • Convulsion • Visual disturbance Case Scenario 9 Manar & Samah

9. Medical Intervensions • The patient received 40mg IV furosemide • Sent to RDU for emergency HD UF 3 kg was removed The patient blood pressure was still uncontrolled Case Scenario 10 Manar & Samah

10. In the ward 11 Manar & Samah

11. 14-16/3/2008BP: 180-186/106-114 mmHg • SLE and ESRD:same medications • HTN: Labetalol 200 mg PO QID Metoprolol 100 mg PO TID Clonidine 200 mcg PO TID Nifedipine LA 60 mg PO TID Furosemide 40 mg IV BID Case Scenario 12 Manar & Samah

12. 17/3/2008 BP: 210/110 mmHg • SLE and ESRD:same medications • HTN: Labetalol 200 mg PO QID Clonidine 200 mcg PO TID Nifedipine LA 60 mg PO TID Furosemide 40 mg IV BID Labetalol 400 mg PO QID Plan: transfer to ICU for IV medications Case Scenario 13 Manar & Samah

13. ICU 14 Manar & Samah

14. ECG Case Scenario 15 Manar & Samah

15. 17/3/2008 ICU <180/120 mmHg HTN Urgency • SLE and ESRD:same medications • HTN: Labetalol 400 mg PO QID Clonidine 200 mcg PO TID Nifedipine LA 60 mg PO TID Furosemide 40 mg IV BID Clonidine 300 mcg PO TID Enalapril 20 mg PO BID Nitroglycerin 200 mcg/ml IV infusion Case Scenario 16 Manar & Samah

16. 18/3/2008 ICU 18/3/2008 ICU BP: 130-155/80-95 mmHg • SLE and ESRD:same medications • HTN: Labetalol 400 mg PO QID Clonidine 300 mcg PO TID Nifedipine LA 60 mg PO TID Furosemide 40 mg IV BID Enalapril 20 mg PO BID Nitroglycerin 200 mcg/ml IV infusion Nifedipine LA 90 mg PO TID Case Scenario Plan: transfer to the floor 17 Manar & Samah

17. 19/3/2008 BP: 134/92 mmHg The patient BP was controlled so the patient discharged on the same medications Labetalol 400 mg PO QID Clonidine 300 mcg PO TID Nifedipine LA 90 mg PO TID Enalapril 20 mg PO BID Case Scenario 18 Manar & Samah

18. Past medications vs Discharged medications Past medications Discharged medications Metoprolol 100 mg PO TID Labetalol 400 mg PO QID Clonidine300 mcg PO TID Clonidine 200 mcg PO TID Nifedipine LA 90 mg PO TID Nifedipine LA 60 mg PO TID Case Scenario Enalapril 20 mg PO BID 19 Manar & Samah

19. Hypertensive Crisis 20 Manar & Samah

20. Systolic BP (SBP) > 179 mm Hg or a diastolic BP (DBP) >109 mm Hg “HYPERTENSIVE CRISIS” “Hypertensive Emergencies” “Hypertensive Urgencies” Presence of acute end-organ damage Absence of acute target-organ involvement Important in formulating a therapeutic plan BP should be lowered immediately, although not to “normal” levels BP should be reduced within 24 to 48 h 21

21. End Organ Damage • Hypertensive encephalopathy • Acute aortic dissection • Acute coronary syndrome • Pulmonary edema with respiratory failure • Severe pre-eclampsia, HELLP syndrome, eclampsia • Acute renal failure • Microangiopathic hemolytic anemia 22 Manar & Samah

22. Development of HypertensiveEmergency • The failure to adhere to prescribed antihypertensive regimens • Inadequate control of BP • The lack of a primary care physician 23 Manar & Samah

23. Autoregulationis a specific form of homeostasis used to describe the tendency of the body to keep blood flow constant when blood pressure varies Normotensive Organ Blood Flow Hypertensive Mean Arterial Blood Pressure (mmHg) 24 Manar & Samah

24. Managment • The preferred agents include labetalol, esmolol, nicardipine, and fenoldopam • Oral and sublingual nifedipine are potentially dangerous in patients with hypertensive emergencies and are not recommended • Clonidine and angiotensin-converting enzyme (ACE) inhibitors are long acting and poorly titratable 25 Manar & Samah

25. Labetalol Labetalol is a combined selective a1-adrenergic and nonselective b-adrenergic receptor blocker with an alfa to beta blocking ratio of 1:7 The onset of action within 2-5 min Duration of action 2-4 hours Labetalol maintains cardiac output Cerebral, renal, and coronary blood flow are also maintained 26 Manar & Samah

26. Nicardipine Nicardipine is a second-generation dihydropyridine derivative calcium-channel blocker with high vascular selectivity and strong cerebral and coronary vasodilatory activity The onset of action within 5-15 min Duration of action 4-6 hours IV nicardipine has been shown to reduce both cardiac and cerebral ischemia 27 Manar & Samah

27. Esmolol Esmolol is an ultrashort-acting b1-adrenergic blocking agent The onset of action within 60 sec Duration of action 10 to 20 min The metabolism of esmolol is via rapid hydrolysis of ester linkages by RBC esterases and is not dependant on renal or hepatic function “ideal b–adrenergic blocker” for use in critically ill patients 28 Manar & Samah

28. Fenoldopam It mediates peripheral vasodilation by acting on peripheral dopamine-1receptors The onset of action 5 min Duration of action30 to 60 min No rebound hypertension Fenoldopam improves creatinine clearance in severely hypertensive patients with both normal and impaired renal function 29 Manar & Samah

29. Nitroprusside It is a very potent arterial and venous vasodilator that decreases both afterload and preload The onset of action seconds Duration of action1 to 2 min • Intraarterial BP monitoring is recommended • It requires special precaution to prevent severe toxicity and adverse events • It requires special handling to prevent its degradation by light Factors limiting the use of nitroprusside: 30

30. Nitroprusside • Contraindications: • Increased intracranial pressure • Coronary artery disease • Hepatic or renal impairment Nitroprusside decreases blood flow Increased risk of cyanide toxicity Cyanide (toxic) Thiocyanate (less toxic) Thiosulfate Liver Nonenzymatically release Nitroprusside Kidney excretion 31 Manar & Samah

31. Nitroprusside • Precautions: • The drug should only be used when other IV antihypertensive agents are not available and in certain circumstances and in patients with normal kidney and liver function • The duration of treatment should be as short as possible • infusion rate should not be > 2 mcg/kg/min 32 Manar & Samah

32. Clevidipine It is third-generation dihydropyridine calcium channel blocker with an ultrashort-acting selective arteriolar vasodilator properties It reduces afterload without affecting cardiac filling pressures or causing reflex tachycardia It is rapidly metabolized by RBC esterases. Thus, its metabolism is not affected by renal or hepatic function 33 Manar & Samah

33. Nifedipine It has been widely used via oral or sublingual administration in the management of hypertensive emergencies But Sublingual Oral It is poorly soluble and is not absorbe through the buccal mucosa Rapidly absorbed from the GI tract after the capsule is broken or dissolved This rout is not FDA approved 34 Manar & Samah

34. Nitroglycerin It is a potent venodilator and only at high doses affects arterial tone Nitroglycerin reduces BP by reducing preload and cardiac output It causes hypotension and reflex tachycardia Low-dose administration (60 mg/min) may be used as an adjunct to IV antihypertensive therapy in patients with hypertensive emergencies associated with acute coronary syndromes or acute pulmonary edema 35 Manar & Samah

35. Hydralazine It is a direct-acting vasodilator Following IM or IV administration, there is an initial latent period of 5 to 15 min followed by a progressive and often precipitous fall in BP that can last up to 12 h It is best avoided in the management of hypertensive crises 36 Manar & Samah

36. SpecialConditions Manar & Samah

37. AcuteAorticDissection Treatment: Drug of Choice If vasodilator alone: reflex tachycardia increase aortic ejection velocity promote dissection propagation Alternative Vasodilator Nitroprusside Nicardipine fenoldopam b-blocker Esmolol Metoprolol 38 Manar & Samah

38. Cerebrovascular Accidents Cerebral Ischemia • withhold antihypertensive therapy for acute ischemic stroke unless • planned thrombolysis • evidence of concomitant noncerebral acute organ damage • if the BP is excessively high, a SBP 220 mm Hg or a DBP 120 mm Cerebral Hemorrhage 39 Manar & Samah

39. Cerebrovascular Accidents Cerebral Hemorrhage • The controlled lowering of the BP is currently recommended only when • SBP is > 200 mm Hg • DBP is > 110 mm Hg • MAP is > 130 mm Hg Nicardipine has been demonstrated to be an effective agent for the control of BP in patients with intracerebral hemorrhage 40 Manar & Samah

40. Preeclampsia / Eclampsia Initial treatment for preeclampsia Magnesium sulfate for seizure prophylaxis Nitroprusside and ACE inhibitors are contraindicated in pregnant patients IV labetalol or nicardipine Blood pressure control Volume expansion 41 Manar & Samah

41. Summary • Hypertensive crisis is medical emergency that requires immediate treatment • Target-organ damage differentiates emergency versus urgency • Hypertensive emergency should be treated with parenteral medications of rapid onset of action and short duration • Blood pressure should not be rapidly reduced 42 Manar & Samah

42. Thank You Manar & Samah