the management of

DIURETIC RESISTANCE IN HEART FAILURE Rully Roesli Bandung

DIURETIC RESISTANCE IN HEART FAILURE

The KIDNEY drown the HEART

The KIDNEY and the HEART drown together

Diuretic Resistance: What is it?

O Inadequate response to diuretic therapy
O Represents an extension of cardiorenal

syndrome O Failure to respond to IV loop diuretics O Decreased efficacy of diuretics with prolonged treatment

Causes of Diuretic Resistance

CARDIO RENAL SYNDROME

Ronco, C. et al. J Am Coll Cardiol 2008;52:1527-1539

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

PATHOPHYSIOLOGY

TOTAL BODY AUTOREGULATION (GUYTON)

CARDIO RENAL INTERACTION
poor perfusion
NORMALIZE VOLUME BODY OVERLOAD VOLUME
HEART FAILURE INCREASED NORMALIZE DIURESIS COP COP NORMAL KIDNEY

normal physiology the KIDNEY helps the HEART

INCREASED NORMALIZE PERIPHERAL RESISTANCE PRESSURE NATRIURESIS

INCREASED NORMAL BP BP

INTER ORGAN COMMUNICATION

What happens if the HEART & the KIDNEY didnt communicate well ?

Cardio Renal Syndrome

CARDIO-RENAL SYNDROME (GUYTON REVISITED)

CARDIO RENAL CONSPIRATION
poor perfusion
VOLUME OVERLOAD
HEART FAILURE LOW COP ANURI OLIGOURI

RENAL FAILURE

INFLAMMATION
RAS ALDOSTERONE SNS ACTIVITY NO-ROS dysbalance Inflammatory mediators INCREASED BP Clamping down Sodium retention

CLINICAL SIGNS

CLINICAL SIGNS of CARDIO ~ RENAL SYNDROME

patient with ADHF = Acute Decompensated Heart Failure CHF = Congestive Heart Failure

Risk Factors
- Old age worsen of RENAL FUNCTION - Low Ejection Fraction - Elevated creatinine level - Low Systolic Blood Pressure - Diabetes Mellitus VOLUME OVERLOAD - Hypertension - Use of antiplatelet drugs, diuretics, or beta-blockers
RESISTANCE TO DIURETICS Hyper or hypo- kalemia Hypomagnesemia Hyponatremia

CARDIO-RENAL SYNDROME TARGET OF TREATMENT

poor perfusion
DIURETICS HEART FAILURE

VOLUME OVERLOAD

ANURI OLIGOURI (VOLUME OVERLOAD)

RENAL FAILURE ULTRAFILTRATION

LOW COP

INFLAMMATION
RAS ALDOSTERONE SNS ACTIVITY NO-ROS dysbalance

ANTI-INFLAMMATION

Clamping down Sodium retention ANTI- RAAS

INCREASED BP

CARDIO-RENAL SYNDROME TARGET OF TREATMENT

poor perfusion VOLUME RENAL ANURI DIURETICS OVERLOAD FAILURE ULTRAFILTRATION OLIGOURI HEART (VOLUME OVERLOAD) FAILURE LOW COP

INFLAMMATION

ANTI-INFLAMMATION

INCREASED BP

RAS ALDOSTERONE SNS ACTIVITY NO-ROS dysbalance

Clamping down Sodium retention

ANTI- RAAS

MANAGEMENT

Managing cardiorenal syndrome: Practical recommendations.

(1) (2) (3) (4) (5) (6) (7) (8) (9)

Restrict fluid and sodium intake Increase furosemide dose Use continuous intravenous furosemide Add thiazides or metolazone Add renoprotective dopamine at 2 3mcg/kg/min Add inotrope or vasodilator (according to systolic blood pressure) Start ultrafiltration Insert intra-aortic balloon pump Insert another device

TARGET OF TREATMENT VOLUME OVERLOAD

Use -type Natriuretic Peptide (BNP=nesiritides) DIURETICS THIAZIDES (HCT) LOOP DIURETICS (furosemide) Effect : -reduce pre/after-load -natriuresis/diuresis -suppress norepinephrine, endotelin, and aldosterone

LFG < 30 cc/mnt

ORAL Diuretic Resistance -Inadequate dose -Excess sodium -Delayed absorption -NSAID -Renal or Heart failure BOLUS DRIP (recommended) may increased risk of renal failure In heart failure patients NEED MORE INVESTIGATION

Change to other LD (bumetanide/torsemide)

Increased oncotic pressure with : Albumin/Mannitol/Colloid

Low-dose Dopamin: Not recommended

Note : diuretics therapy can worsen renal function

Disadvantages of Conventional Diuretic Therapy in CHF

O
O O O O

Has potential to activate neurohormonal vasoconstrictor systems Can cause electrolyte abnormalities Has been associated with increased risk of morbidity and mortality Can lead to development of pre-renal azotemia May result in diuretic resistance

Diuretic Dose
Pharmacokinetics of loop diuretics according to the renal function in heart failure patients. IV: intravenous; CrCl: Creatinine Clearance.
Moderate renal Insufficiency Severe renal Insufficiency Heart Failure

Maximal IV dose (mg)

Diuretic

IV Loading Dose CrCl (mg) <25

ml/min

Infusion rate (mg/hr)

CrCl 2575 ml/min
10 then 20 0.5 then 1 5 then 10

CrCl >75 ml/min

10 0.5 5

Furosemide Bumetanide Torsemide

80160 48 2050

160200 810 50100

4080 12 1020

40 1 20

20 then 40 1 then 2 10 then 20

Keberhasilan terapi diuretik dapat diramalkan dari Warna dan konsentrasi urin

TARGET OF TREATMENT INREASED RAAS

Use of ACE-I OR ARB
Start with low dose Patient not dehydrated Avoid using NSAID

If contraindicated

Hydralazine/ Isosorbid-dinitrates ISORDIL

increased creatinine Combination with CCB

increased potassium Combination with DIURETICS

BETTER OUTCOME
(SOLVD,PRIME-2,CONSENSUS,ELITE)

When using of ACE-I OR ARB beware of : increased creatinin and potassium

TARGET OF TREATMENT FUTURE DRUGS

Arginine Vasopressin Receptor Antagonists (Conivaptan or Tolvaptan) - antagonist the arginine vasopressin secreted by pituitary gland - results in diuresis and retention of electrolytes Adenosine A1 Receptor Antagonists (Conivaptan or Tolvaptan) - antagonist plasma adenosine - results in diuresis and natriuresis

ULTRAFILTRATION

TARGET OF TREATMENT : ULTRAFILTRATION SEVERE VOLUME OVERLOAD

iv DIURETICS

DIURETIC RESISTANCE

ULTRAFILTRATION

CRRT
SCUF

SLED

Ultrafiltration in CHF Patients: Principles and Benefits

O Provides an additional modality for fluid

removal O Allows for a predictable amount of fluid to be removed O Rapidly removes salt and water (up to 500 cc/hr) O Safer than diuretics because removal of salt and water is isotonic

Use of Ultrafiltration in CHF

O

Ultrafiltration can be beneficial in

O
O O

Acutely decompensated CHF patients with obvious volume overload Diuretic-resistant patients Renally impaired patients Hospitalized heart failure patients

Multidisciplinary Approach to Successful Adoption of Ultrafiltration

O Many departments/personnel should be

educated and involved

O ICU O IV team

O Nephrologists
O Other cardiologists O Nurses O Emergency department

O Telemetry unit

HYBRID DIALYSIS

IHD

SLED
6 12 100-150 300 Sedang (6-12 jam)

CRRT

IHD
Td (jam) Qb (cc/m) Qd (cc/m) UF (/jam) 4-5 200-300 500 Cepat (4-5 jam) 24 100-150 0 Lambat ( 24 jam)

CRRT

Pilihan dialisis baru :

HFR - SLED

Clinical studies of Ultrafiltration In Heart Failure

Ultrafiltration versus IV Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure (UNLOAD) Trial
O Prospective, randomized trial comparing

ultrafiltration and aggressive IV diuretic therapy in acutely decompensated HF patients O Patients had to have 2 signs of volume overload, be randomized within 24 hours of admission, be hemodynamically stable, and have no prior treatment with IV vasoactive drugs

UNLOAD: Primary Endpoint Results

O At 48 hours, significantly greater amount

of weight loss seen with ultrafiltration (5 kg vs 3.1 kg) as compared to IV diuretics O Dypsnea scores significant and similar in both groups

UNLOAD: Secondary Endpoint Results

O Net fluid loss at 48 hours greater in

ultrafiltration group than standard care group O At 90 days, ultrafiltration resulted in

O 48% in % of patients requiring re-

hospitalizations for HF O 53% in absolute # of re-hospitalizations O 62% in length of re-hospitalizations O 53% in # of emergency department or unscheduled office visits for HF

Ultrafiltration Versus Usual Care for Hospitalized Patients With Heart Failure The Relief for Acutely Fluid-Overloaded Patients With Decompensated Congestive Heart Failure (RAPID-CHF) Trial

47

Relief for Acutely Fluid-Overloaded Patients with Decompensated Congestive Heart Failure (RAPID-CHF) Trial
O Multicenter, randomized trial comparing

the effects of ultrafiltration (n = 20) to usual care (n = 20) in hospitalized patients with decompensated HF O Early ultrafiltration was well-tolerated and resulted in significantly greater weight loss and net fluid removal compared to usual care

Results
Fluid removal after 24 h was 4,650 ml and 2,838 ml in the UF and usual care groups, respectively (p = 0.001) Compared to usual care, UF was not associated with significant changes in heart rate, blood pressure, or electrolytes Dyspnea and CHF symptoms were significantly improved in the UF group compared to usual care at 48 h

Bart et. al. JACC 2005;46:2043-2046 (n=40)

49

Conclusion
The early application of UF for patients with CHF was feasible, well-tolerated, and resulted in significant weight loss and fluid removal.

Bart et. al. JACC 2005;46:2043-2046 (n=40)

50

Early Ultrafiltration in Patients with Decompensated Heart Failure and Observed Resistance to Intervention with Diuretic Agents

The EUPHORIA Trial

51

Early Ultrafiltration in Patients with Decompensated Heart Failure and Observed Resistance to Intervention with Diuretic Agents (EUPHORIA) Trial

O Single center, prospective trial (n = 20)

comparing the safety of reducing length of hospitalization by early ultrafiltration compared with IV diuretics and/or vasoactive drugs in decompensated CHF patients with diuretic resistance O Early ultrafiltration decreased hospital length of stay and number of rehospitalizations; clinical benefits sustained up to 90 days

Conclusion
In heart failure patients with volume overload and diuretic resistance, UF before IV diuretics effectively and safely decreases length of stay and readmissions. Clinical benefits persist at three months.

A treatment strategy of early UF may decrease length of stay and rehospitalizations in high-risk heart failure patients.
Early UF may be an alternative to reserving UF for patients refractory to all other pharmacologic strategies. A prospective randomized study comparing UF with standard therapy for ADHF to identify effects specifically attributable to UF (UNLOAD) is complete and awaiting publication 2006.
Costanzo et. al. JACC 2005;46:2047-2051 (n=20) 53

Circ Heart Fail 2009 ;2

SEMOGA BERMANFAAT

HATUR NUHUN