台大醫院雲林分院 黃道民 Tao-Min Huang NTUH Yun-Lin Branch Acute Cardio-renal Syndrome.

A clinical scenario. A 62-year-old man PHx: DM, type 2 CKD, stage III ICMP, NYHA Fc II CC: 1 week of progressive dyspnea and weight gain. PE: BP: 118/70mmHg; HR = 82 bpm Basilar rales Bilateral pitting edema.

A clinical scenario. ECG: NSR N-Terminal pro-BNP = 16,500 pg/mL (0-450 pg/mL) CK, CK-MB, Tr. I: WNL UN = 38mg/dL; Cre = 2.0mg/dL (Baseline mg/dL) U/A, renal sonography: unremarkable CXR

Chest film.

Treatment. IV bolus Furosemide 20mg q6h U/o = 500ml/day Continous Furosemide U/O = 300ml/day Cre = 2.2mg/dL Spironolactone and lisinopril were held. U/O = 100ml/day Orthopnea aggravated. Nephrologist consultation for RRT

A Common scenario in Critical Care.

Epidemiology

Severity of WRF. Gottlieb et al., J Card Fail. 2002;8(3):136

How to define WRF Gottlieb et al., J Card Fail. 2002;8(3):136

Worsening Renal Function Forman et al. J Am Coll Cardiol. 2004;43(1):61 1. WRF: defined with ≥0.3mg/dL elevation of SCr patients admitted to hospital.

Mid-Term Survival Am Heart J Aug;150(2):330

Adjusted HR for ESRD: 147,007 AMI Elderly. Arch Intern Med May 12;168(9):987

Adjusted HR for All Cause Death: 147,007 AMI Elderly. Arch Intern Med May 12;168(9):987

Cox’ Proportional Survival Function: 147,007 AMI Elderly Arch Intern Med May 12;168(9):987

WRF: a meta-analysis J Card Fail Oct;13(8):599 All Cause Mortality HR = 1.62

J Card Fail Oct;13(8):599

WRF in ADHF Incidence: 19-45% Negative outcome predictor in: Short- and long-term all-cause and cardiovascular mortality Prolonged duration of hospitalization Increased readmission rates Accelerated progression to ESRD Higher healthcare costs Eur Heart J Mar;31(6):703

Pathophysiology. (a) Adequacy of arterial filling and renal perfusion (b) Degree of venous congestion (c) Raised intra-abdominal pressure.

Pathophysiology: Low cardiac output. Heart 2010;96:255

Not all CRS are equal. J Am Coll Cardiol Jan 3;47(1):76

Mortality between preserved/reduced Renal Function. J Am Coll Cardiol Jan 3;47(1):76 O.R. = 2.45 (Diastolic) vs (Systolic)

Congestion and WRF: not novel findings J Physiol Jun 6;72(1):49

CVP is better predictive. J Am Coll Cardiol 2009;53:589

Which is more important? Congestion or WRF? (+) WRF (+) Congestion (-) WRF (+) Congestion (-) WRF (-) Congestion (-) WRF (-) Congestion (+) WRF (-) Congestion 1 year Death or reTx. Circ Heart Fail Jan 1;5(1):54

Which is more important? Congestion or WRF? (+) WRF (+) Congestion (-) WRF (+) Congestion (-) WRF (-) Congestion (-) WRF (-) Congestion (+) WRF (-) Congestion 1 year Death, HF readmission, or reTx. Circ Heart Fail Jan 1;5(1):54

Intra-Abdominal Pressure David J.J. Muckart, MD, University of Natal Medical School

IAP and Mortality Crit Care Med 2005; 33:315

IAP and Mortality Crit Care Med 2005; 33:315

IAP and Change of Cre. J Am Coll Cardiol Jan 22;51(3):300

Congestion? Kidney Injury? WRF (or CRS type 1) is bad. Congestion (high filling pressure, fluid overload) is bad. But WRF is not associated with (so much) hazard, after adjustment of “Congestion.”

De-congestive therapy.

Diuretics Patients admitted with evidence of significant fluid overload should initially be treated with loop diuretics, usually given intravenously. Early intervention has been associated with better outcomes for patients hospitalized with decompensated HF. ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults. Circulation. 2009;119(14):1977

Diuretics and BNP: AEHERE registry 58,465 ADHF episodes. J Am Coll Cardiol Aug 12;52(7):534

Factors predicting in-hospital death: Early Diuretics is Important. J Am Coll Cardiol Aug 12;52(7):534

Sub-clinical fluid retention. Adamson et al. J Am Coll Cardiol. 2003;41(4):565

Sub-clinical fluid retention. Adamson et al. J Am Coll Cardiol. 2003;41(4):565

Benefit of De-congestion therapy. Symptom improvement Cardiopulmonary function Myocardial structure Re-hospitalization rates Am J Kidney Dis. 2011;58(6):1005

Loop Diuretics: Continuous or Intermittent? J Am Coll Cardiol Aug;28(2):376

Loop Diuretics: Continuous or Intermittent? J Am Coll Cardiol Aug;28(2):376

Loop Diuretics: Cont. or Bolus? 24hrs’ urine Cochrane Database Syst Rev. 2005:20;(3):CD

Loop Diuretics: Cont. or Bolus? All Cause Mortality Cochrane Database Syst Rev. 2005:20;(3):CD

Loop Diuretics: Cont. or Bolus? Significant e- change Cochrane Database Syst Rev. 2005:20;(3):CD

Loop Diuretics: Cont. or Bolus? Hearing Loss Cochrane Database Syst Rev. 2005:20;(3):CD

Loop Diuretics: Cont. or Bolus? Increased SCr. Cochrane Database Syst Rev. 2005:20;(3):CD

How to Prescribe Diuretics in ADHF: DOSE Study Dose: High dose: total daily intravenous furosemide dose 2.5 times their total daily oral loop diuretic dose in furosemide equivalents Standard Dose: total intravenous furosemide dose equal to their total daily oral loop diuretic dose in furosemide equivalents Route: Bolus Every 12 hours. (Q12H) Continuous Randomized to 4 groups (1:1:1:1) Felker et a. N Engl J Med. 2011;364(9):797

Loop Diuretics: Dose? Continuous? Global VAS Score Felker et a. N Engl J Med. 2011;364(9):797

Loop Diuretics: Dose? Continuous? Composite Outcomes Felker et a. N Engl J Med. 2011;364(9):797

Complications: DOSE Felker et a. N Engl J Med. 2011;364(9):797

Limitations of DOSE. Primary endpoint: Global assessment of symptoms. Underpowered to detect other clinical outcomes. In addition, bolus group tended to receive a higher total dose Supine position may promote diuresis Felker et a. N Engl J Med. 2011;364(9):797

Diuretics Resistance When diuresis is inadequate to relieve congestion, as evidenced by clinical evaluation, the diuretic regimen should be intensified using either: Higher doses of loop diuretics; Addition of a second diuretic (such as metolazone, spironolactone or intravenous chlorothiazide); or Continuous infusion of a loop diuretic. (Level of Evidence: C) ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults. Circulation. 2009;119(14):1977

Ultrafiltration

Concept of Ultrafiltration.

Removal of Fluids with UF. RAPID-CHF. J Am Coll Cardiol Dec 6;46(11):2043

Fluid removal and Weight. RAPID-CHF. J Am Coll Cardiol Dec 6;46(11):2043

UNLOAD UNLOAD. J Am Coll Cardiol. 2007;49(6):675

Loop Diuretics: Neurohormon activation. After single bolus injection of fursemide in 15 patients with chronic heart failure: 20 mins later: SVI LV filling Heart rate MAP SVRI PRA Plasma norepinephrine Plasma arginine vasopressin 3.5 hrs later: Rreturned toward the control levels. Ann Intern Med Jul;103(1):1-6

Loop Diuretics and Vasodilators: Neurohormon activation. J Am Coll Cardiol May 15;39(10):1623

Loop Diuretics and Vasodilators: Neurohormon activation. J Am Coll Cardiol May 15;39(10):1623 Fig. Effect of therapy on plasma aldosterone levels (left) and plasma renin activity (right) before intervention (A), after intravenous vasodilators and diuretics (B) and after transition to an oral regimen, including captopril (C). *p 0.05 compared to A.

Ultrafiltration: Less neurohormon activation. Am J Med Mar;96(3):191-9.

Composition of Urine: Sodium (Na) Congest Heart Fail. 2009;15(1):1-4.

Composition of Urine: Potassium (K) Congest Heart Fail. 2009;15(1):1-4.

Composition of Urine: Magnesium (Mg) Congest Heart Fail. 2009;15(1):1-4.

Symptom control: RAPID-CHF Trial. RAPID-CHF. J Am Coll Cardiol. 2005;46(11):2043

Symptom Control: UNLOAD Study UNLOAD. J Am Coll Cardiol. 2007;49(6):675-83

Electrolyte disturbance UNLOAD. J Am Coll Cardiol. 2007;49(6):675-83

Hypotension. UNLOAD. J Am Coll Cardiol. 2007;49(6):675-83

J Card Fail Dec;12(9):707

Clinical adverse events. J Card Fail Dec;12(9):707

Elevated Creatinine (AKI?) J Card Fail Dec;12(9):707

AKI (SCr change) in UNLOAD UNLOAD. J Am Coll Cardiol. 2007;49(6):675-83

Ultrafiltration improves renal function? J Card Fail Aug;14(6):531-2

Reduction of IAP J Card Fail Aug;14(6):508

Reduction of IAP J Card Fail Aug;14(6):508

Congestion Inadequate Venous filling Abdominal Pressure

Cost. Circ Cardiovasc Qual Outcomes Nov;2(6):566

Commercialized UF machine

Aquapheresis Summary.

Current Setting in YL branch. Machine: HF 440 Indication: CHF and diuretics resistance (Bumetanide > 1mg/hr) UF: 1000cc/hr Net UF: cc/hr Pre dilution: 70% No anticoagulation

Summary of UF vs. Diuretics. Neurohormonal activation. Efficient Na removal. K/Mg wasting. Cost Mechanical complication Easy to apply. Bleeding issue. Unknown. Survival Re-admission rate Length of stay Symptom control Hypotension

Ultrafiltration “Ultrafiltration is reasonable for patients with refractory congestion not responding to medical therapy” ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults. Circulation. 2009;119(14):1977

A clinical scenario. UF with HF440 was done for 2 days with heparinization. A total of 4000cc water was removed using CVVH. Patients symptom improved and u/o increased to baseline. At discharge, UN = 32mg/dL Cre = 1.8mg/dL BW: comparable to basline

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