The Art and Science of Diuretic therapy

Transcription

1 The Art and Science of Diuretic therapy Dr. Fayez EL Shaer Associate Professour of cardiology Consultant cardiologist MD, MSc, PhD, CBNC, NBE FESC, ACCP, FASNC,HFA KKUH, KFCC

2 Heart failure: fluid overload

3 Diuretics in the context of HF therapy

4 Clinical symptoms of fluid retention Oedema (preferably legs: grading ankle/calf/thigh) Pulmonary rales Raised jugular venous pressure Hepatomegaly/hepatojugular reflux Pleural effusion Ascites Additional diagnostic workup to identify fluid retention: X- ray, echocardiography, abdominal ultrasound Camm AJ, et al. The ESC Textbook of Cardiovascular Medicine. 2nd ed. 2009;851-8.

5 Goal of diuretic The goal of diuretic treatment in heart failure is not simply to increase urinary excretion of sodium chloride, but : 1- Achieve negative short-term sodium chloride and water balance (here termed decongestion). 2- In the longer term, to reduce extracellular fluid volume.

6 Diuretics in :Impact on morbidity?

7 Neuroendocrine effects of diuretics in CHF

8 Loop diuretic: good Block NKC absorption in ascending limb of loop of Helene. Block NKC in the vascular smooth muscle cause VD. Inhibit tubule- glomerular feedback, so, this effect lead to increase in glomerular filtration rate. Increase the level of prostaglandin in the proximal tubules increase GFR.

9 Bad Block NKC in the macula densa which stimulate secretion of renin ( bad ). Ceiling, need he drug to be above the naturesis threshold for longer time. Post diuretic sodium retention : there low sodium excretion in between the doses. Braking phenomenon: diuretic response is reduced with subsequent does of diuretic dose, due to activation of RAAS, activation of sympathetic, nephron remolding, depletion of extracellular volume. Nephron remolding: stimulation of distal nephron to augment sodium reabsorption.

10 Pharmacologic effect Ceiling. Post-diuretic sodium retention. Braking phenomenon. Nephron Remodeling. Rebound.

11 Diuretics have complex effects on renal and systemic hemodynamics, which are influenced by the dose and route of administration, concomitant disease and treatment, and longterm use.

12 Diuretic effects on RAAS

13 Initiation of diuretic therapy Diuretics are recommended in patients with HF and clinical signs or symptoms of congestion. Check renal function and serum electrolytes. Start with thiazide, but most patients will receive loop diuretics due to higher efficacy to induce diuresis and natriuresis. Salt restriction is required to ensure diuretic effect. Self adjustment of diuretic dose can be based on daily weight measurements on HF outpatients. Basal regular drug intake should be pursued to avoid severe fluctuations in fluid retention due to over-compensation mechanisms.

14 Diuretic monitoring: Regular drug intake to maintain efficacy (to prevent rebound and increased fluid retention in drug-free intervals). Minimum dose to achieve diuresis and manage congestion should be used to minimize adverse effects Side effects from multi-drug therapy (hyperkalaemia exacerbated by additional ACE-I therapy) Regular (daily) weight measurement to ensure stable fluid balance

15 Potential problems with diuretic therapy

16 Differential diagnosis: hyponatraemia in heart failure

17 Diuretic resistance Defined as the failure of diuretics to achieve decongestion, which is manifest by a low urine sodium concentration, despite the use of maximal recommended doses. Continuous infusion of diuretic therapy is frequently used in such patients.

18 When diuretics do not achieve decongestion despite the use of maximal doses, the patient is typically said to be diuretic resistant. Single doses of furosemide (250 mg) are often considered to be maximal, although recommendations vary.

19 Diuretic-resistant patients are at high risk for illness and death, and this scenario, which is frequently associated with kidney dysfunction, is often termed the cardiorenal syndrome.

20 Causes of Diuretic Resistance. Inadequate dose of diuretic Non adherence.( Not taking drug. High sodium intake ). Pharmacokinetic factors 1- Slow absorption of diuretic because of gut edema 2- Impaired secretion of diuretic into the tubule lumen 1- Chronic kidney disease 2- Aging 3- Drugs ( NSAID, Probenecid)

21 Hypoproteinemia Hypotension Nephrotic syndrome Antinatriuretic drugs (NSAID, Antihypertensive agents) Low renal blood flow Nephron remodeling Neurohormonal activation

22 Diuretics in severe congestion?

23 I.V. diuretics in acute HF:

24 Management of diuretic resistance

25 DOSE-HF (n=308) 25 High dose associated with greater diuresis but higher creatinine COMPOSITE END POINT* *Global assessment of symptoms (VAS), change in serum creatinine Felker et al NEJM 2011;364; :23:52 AM

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28 CARdiorenal REScue Study in Acute Decompensated Heart Failure (CARESS-HF) Prospective, randomized trial Primary endpoint Change in scr and weight together as a bivariate endpoint assessed at 96 hrs post enrollment Secondary Endpoint PE assessed at days 1-3 and 7 days Treatment failure, weight and fluid loss, clinical decongestion, peak scr, change in electrolytes, LOS, biomarkers, change in diuretic doses all at various time points

29 Diuretic regimen in CARESS HF Diuretic Grid Suggested Dose Current Dose Daily Loop Dose Thiazide A <80 mg 40 mg IV bolus + 5 mg/h None B mg 80 mg IV bolus + 10 mg/h C mg 80 mg IV bolus + 20 mg/h D >240 mg 80 mg IV bolus + 30 mg/h 5 mg metolazone once daily 5 mg metolazone twice daily 5 mg metolazone twice daily

30 Diuretic regimen in CARESS HF Daily assessment of Urine output (UO) UO >5 L/d Reduce current diuretic regimen if desired UO 3 5 L/d Continue current diuretic regimen UO <3 L/d Advance to next After 48 Hrs Consider dopamine or dobutamine at 2 mg/kg/h if SBP <110 mm Hg and EF < 40% or RV systolic dysfunction. Consider nitroglycerin or nesiritide if SBP >120 mm Hg (any EF) and severe symptoms H Consider hemodynamic guided IV therapy, LVAD, dialysis, or ultrafiltration crossover

31 Changes in Serum Creatinine and Wt at 96 H (Bivariate Response)

32 Change in serum creatinine

33 Body weight change

34 Conclusion The use of a stepped pharmacologictherapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events

35 Torasemide on outcome in HF The TORasemide In Congestive heart failure (TORIC) study

36 MRA improve outcome in HF: The RALES trial (NYHA class III IV)

37 MRA improve outcome in HF: The EPHESUS and EMPHASIS trial

38 The UNLOAD Study The UNLOAD :Study 200 patients (100 each arm) randomized, multi-center study comparing ultrafiltration versus standard care for acutely decompensated patients Superior salt & water removal/weight loss At 48 hours, ultrafiltration demonstrated 38% greater weight loss 28% greater net fluid loss Improved Dyspnea score At 90 days, reduced readmissions 50% reduction in re-hospitalization episodes 63% reduction in total re-hospitalized days 52% reduction in unscheduled clinic/er visits Costanzo MR et al. J Am Coll Cardiol. 2007;49:

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40 Tolvaptan The oral vasopressin-2 receptor antagonist tolvaptan inhibits the action of antidiuretic hormone and increases excretion of free water(aquaresis).

41 Outcome Study with Tolvaptan (EVEREST), which evaluated patients who were hospitalized for heart failure (with or without hyponatremia), did not show superiority of tolvaptan over placebo with respect to long-term clinical outcomes, although potentially beneficial effects with respect to volume status and symptoms were observed in the study group.

42 Dopamine Low renal blood flow contributes to sodium retention in ADHF by limiting sodium filtration, increasing sodium reabsorption, and reducing renal delivery of diuretics to the proximal tubule. Since dopamine increases renal blood flow and excretion of urinary sodium at low doses, it might therefore augment natriuresis. Similar, considerations apply to natriuretic peptides.

43 ROSE-AHF trial, 360 patients who were hospitalized for ADHF with impaired renal function were randomly assigned to furosemide plus dopamine infusion (at a dose of 2 μg per kilogram of body weight per minute), nesiritide (at a dose of μg per kilogram per minute), or placebo. Neither active drug affected the primary end points of urine volume or change in cystatin C level during the ensuing 72 hours.

44 Conclusion Skillful use of diuretic therapy remains fundamental to the successful management of heart failure. Understanding the physiological effects as well as the pharmacokinetic and pharmacodynamic properties of these drugs is key for safe and effective use.

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46 I.V. diuretics in acute heart failure

47 Commonly used diuretics and dosages