nitrate as first line monotherapy for pulmonary oedema

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  1. 1. Nitrate as First Line Monotherapy for Pulmonary Oedema EVIDENCE BASED GUIDELINES Dr. Anwer G Almosewi
  2. 2. Definition: Leakage of fluid from the pulmonary capillaries and venules into the alveolar space as a result of increased hydrostatic pressure PULMONARY EDEMA
  3. 3. Cardiogenic Oedema In congestive cardiac failure, oedema occurs as a result of an increase in the pulmonary venous pressure.
  4. 4. Non-Cardiogenic Oedema In non-cardiogenic oedema, there is usually minimal elevation of pulmonary capillary pressure, except in volume overload due to oliguric renal failure. altered alveolar-capillary membrane permeability, : (ARDS), lymphatic insufficiency: lung transplant or lymphangitic carcinomatosis. diminished plasma oncotic pressure in hypoalbuminemic states : Negativity of interstitial pressure following the rapid removal of pneumothorax. Unknownmechanisms : narcotic overdose, high-altitude or neurogenic pulmonary oedema.
  5. 5. PATHOPHYSIOLOGY 1. increased preload 2. increased afterload 3. decreased LV function
  6. 6. GOALS OF TREATMENT 1. decrease preload 2. decrease afterload 3. improve LV function
  7. 7. Note More than 50% of patients with cardiogenic pulmonary edema are euvolemic. Treatment should be based not necessarily on fluid removal, but on fluid redistribution.
  8. 8. PRELOAD REDUCTION Traditional treatment Morphine Furosemide Nitrates
  9. 9. FUROSEMIDE Preload reduction Diuresis " increased afterload causes decreased RBF " delayed effect: 30 120 minutes Direct vasoactivity " venodilation little evidence
  10. 10. FUROSEMIDE In most patients, diuresis does not occur for at least 20-90 minutes; therefore, the effect is delayed. Diminished renal perfusion in CPE may delay the onset of effects of loop diuretics
  11. 11. FUROSEMIDE Francis, et al (Ann Intern Med, 1985) Early adverse hemodynamic effects " 20 minutes after administration significant increase in HR, SVR (afterload) significant decrease in SV Gradual return to baseline with diuresis
  12. 12. FUROSEMIDE ! Kraus, et al (Chest, 1990) Effects of IV furosemide on PCWP over 1 hour in patients receiving nitrates and/or captopril Furosemide alone or furosemide plus nitrates " increase in PCWP over initial 15 minutes " then decrease PCWP with diuresis If premedicated with nitrates plus captopril " immediate and sustained decrease PCWP
  13. 13. American College of Emergency Physicians (ACEP) recomendations Level B recommendations. Treat patients with moderate- to-severe pulmonary edema resulting from acute heart failure with furosemide in combination with nitrate therapy. Level C recommendations. Aggressive diuretic monotherapy is unlikely to prevent the need for endotracheal intubation compared with aggressive nitrate monotherapy. Diuretics should be administered judiciously, given the potential association between diuretics, worsening renal function
  14. 14. FUROSEMIDE Nelson, et al (Eur Heart J, 1983) IV furosemide (1 mg/kg) administration in AMI patients with LV failure Initial adverse hemodynamic effects " decreases in CO and SV during initial 90 minutes Parameters returned to baseline over next 60 90 minutes
  15. 15. FUROSEMIDE Invasive hemodynamic monitoring During the next 1 to 2 hours, the patients receiving lasix experienced worsening hemodynamics, including increased SVR, increased left ventricular lling pressures, and a decrease in stroke volume Other Class II and III studies have similarly reported improved hemodynamics after nitrate administration and transiently worsening hemodynamics for 1 to 2 hours after treatment with furosemide
  16. 16. FUROSEMIDE Class III study : Butler J et al. Am Heart J. 2004 : demonstrated an association between diuretic use and worsening renal function. several recent studies have identied an association between impaired renal function and increased mortality among acute heart failure syndrome patients . ADHERE: JAMA. 2005: 60,000 patients:mortality is greater than 20% , Krumholz et al J Card Fail. 2003 : 1,681 patients : mortality 3 times
  17. 17. SUMMARY FUROSEMIDE Decreases preload through diuresis Delayed effect No consistent data regarding immediate direct preload reducing effect Initial adverse hemodynamic effects - Increased SVR - Decreased SV, CO
  18. 18. CONCLUSION - FUROSEMIDE Furosemide should be considered a third-line medication in the treatment of cardiogenic pulmonary edema!
  19. 19. MORPHINE Advantages Histamine effect causes decrease in preload Anxiolysis may decrease catecholamines " decrease afterload
  20. 20. MORPHINE Disadvantages Side-effects may increase catecholamines " rash/urticaria from histamine release " nausea/vomiting Respiratory depression with high doses Concerns if patient has low blood pressure " myocardial depressant Limited evidence (none?) to support direct hemodynamic benefits
  21. 21. MORPHINE Timmis, et al, (Br Med J, 1980) 15 and 45 minutes after injection, BP, HR, and CI decreased No decrease in preload
  22. 22. MORPHINE Hoffman, et al (Chest, 1987 46% objective deterioration No patients receiving NTG without morphine had deterioration
  23. 23. MORPHINE Peacock WF, et al (Emerg Med J, 2008) Morphine vs. no morphine for acute decompensated heart failure independent predictor of mortality (OR 4.84) " increased need for mechanical ventilation, ICU admission, prolonged hospitalization
  24. 24. MORPHINE Anxiolysis Decrease in catecholamines, afterload Why not use a benzodiazepine??? " no concerns with rash/urticaria " no concerns with nausea/vomiting " no concerns with respiratory depression " no concerns with hypotension
  25. 25. SUMMARY MORPHINE Preload reduction Nitrates are superior Anxiolysis Side-effect profile favors benzodiazepines
  26. 26. CONCLUSION MORPHINE Morphine has no role in the treatment of cardiogenic pulmonary edema!
  27. 27. NITROGLYCERIN Nitroglycerin vs. furosemide for preload reduction Cotter, et al (Lancet, 1998) Beltrame, et al (J Card Fail, 1998) Kraus, et al (Chest, 1990) Hoffman, et al (Chest, 1987) Nelson, et al (Lancet, 1983)
  28. 28. NITROGLYCERIN Advantages Rapid, reliable preload reduction Moderate/high doses reduce SVR (afterload) " maintains or improves SV and CO Multiple forms of administration topical, SL, IV (be aggressive!) Short half-life; especially important if prehospital misdiagnosis
  29. 29. NITROGLYCERIN Caution in the presence of Hypotension Acute mitral regurgitation Aortic stenosis Pulmonary hypertension Patients taking sildenafil
  30. 30. NITROGLYCERIN Cotter et al,Lancet. 1998 : 104 patients with severe, acute heart failure high-dose nitrates with low-dose furosemide was a more effective than low-dose nitrate and high-dose furosemide . The combined endpoint of hospital death, myocardial infarction within 24 hours, and intubation within 12 hours was signicantly lower in the high-dose nitrate group (25% versus 46% - Intubation: (13% versus 40%)
  31. 31. American College of Emergency Physicians (ACEP) recomendations Level B recommendations. Administer intravenous nitra therapy to patients with acute heart failure syndromes and associated dyspnea.
  32. 32. SUMMARY - NITROGLYCERIN Better than morphine or furosemide for preload reduction Safer than morphine or furosemide in prehospital setting SL nitroglycerin provides rapid and effective initiation of treatment Followed by topical NTG if moderate CPE Followed by IV NTG if severe CPE
  33. 33. CONCLUSION -NITROGLYCERIN Nitroglycerin should be first-line prehospital and emergency department treatment for moderate CHF and pulmonary edema.
  34. 34. Nesiritide Human BNP that decreases PCWP, pulmonary artery pressure, RA pressure, and systemic vascular resistance while increasing the cardiac index and stroke volume index.
  35. 35. Nesiritide Therapy with nesiritide has decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels and has reduced ventricular ectopy and ventricular tachycardia
  36. 36. Nesiritide . Investigators compared IV nesiritide with IV NTG. IV nesiritide was associated with some hypotension but was otherwise well tolerated Analysis, which included 5 randomized trials, showed that patients who received nesiritide were more likely than others to have significant renal failure..
  37. 37. Nesiritide increased mortality in the IV nesiritide group compared with the patients receiving IV NTG, although the difference was not statically significant A Meta-analysis of 3 randomized trials of 485 patients receiving nesiritide and 377 patients not receiving nesiritide showed a 7.2% 30-day mortality with nesiritide versus 4% without nesiritide.
  38. 38. AFTERLOAD REDUCTION Results in increased CO, restores renal blood flow Nitroglycerin excellent single agent for simultaneous preload and afterload reduction Nitroprusside " acute mitral regurgitation, severe hypertension Hydralazine ACE-inhibitorsfor acute CPE
  39. 39. ACE-INHIBITORS Barnett, et al (Curr Ther Res, 1991) 25 mg SL captopril if BP > 110 12.5 mg SL captopril if BP < 110 Decreased PCWP (preload) noted by 10 minutes No change in HR, MAP abrupt increase in diuresis without the use of a diuretic! (due to improved renal blood flow)
  40. 40. ACE-INHIBITORS ! Varriale, et al (Clin Cardiol, 1993) Hemodynamic response to 1.25 mg IV enalaprilat in patients with severe CHF and severe MR Increased CO and SV Decreased MAP and SVR (afterload) Decreased PCWP (preload) Decreased the magnitude of MR
  41. 41. ACE-INHIBITORS Langes, et al (Curr Ther Res, 1993) IV captopril infusion in m