I trattamenti extracorporei nello scompenso acuto: ultrafiltrazione e/o emofiltrazione Emilio Assanelli Unità di Terapia Intensiva Cardiologica Trattamento dello scompenso cardiaco acuto e cronico - Milano, 12 Marzo 2014 -
Elementi Caratterizzanti lo Scompenso Cardiaco Ritenzione idro-salina Insufficienza renale Attivazione neuro-ormonale
CRS type I (acute cardiorenal syndrome) Ridotta risposta alla terapia diuretica Ronco C. et al. J Am Coll Cardiol 2008
Interrelation of Humoral Factors, Hemodynamics, and Fluid and Salt Metabolism in Congestive Heart Failure: Effects of Extracorporeal Ultrafiltration Marenzi G. et al. Am J Med 1993
Increase in central venous pressure Reduction in cardiac output and renal blood flow A-V Pressure gradient
Damman K et al. Eur J Heart Fail 2007
Proportional survival (%) 100 90 egfr 80 70 > 76 ml/min 59-76 ml/min 60 50 44-58 ml/min 40 30 < 44 ml/min 0 250 360 500 750 1000 Days Hillege HL et al. Circulation 2000
Marenzi G. et al. Am J Med Sci 2001
Marenzi G. et al. Am J Med Sci 2001
Loop Diuretic Normal 20% 1% RAAS activation
Diuretic dose (mg) and weight loss (kg) Metha RH et al. for the ESCAPE Trial Investigators. Am J Cardiol 2009
Distribution of weight changes during initial hospitalization Metha RH et al. for the ESCAPE Trial Investigators. Am J Cardiol 2009
IMPACT-HF 100 % 80 60 60% n=363 45% 40 25% 20 0 Discharged with dyspnea Worsening HF at 2 months Re-hospitalization at 2 months Am J Cardiol 2004
ACTIV in CHF Severe congestion: dyspnea, JVD, and peripheral edema % 12 2-month mortality 9 8.1% 6 4.9% 3 0 No severe congestion at presentation Severe congestion at presentation Gheorghiade M. et al. JAMA 2004
147 NYHA class IV pts; congestion score to evaluate freedom from congestion at 4-6 weeks posthospitalization: - Orthopnea, - JVD, - >1 Kg weight gain; - diuretic dose, - edema 87% 67% 41% Lucas C et al. Am Heart J 2000
Heart failure and severe fluid overload Congestion Increased CVP Reduction in glomerular filtration Neuro-humoral activation Reduction in sodium excretion and response to loops diuretics
Urinary sodium concentration Levy M. J Clin Invest 1972
Auld RB et al. J Clin Invest 1971
Heart failure and severe fluid overload Congestion Increased CVP Reduction in glomerular filtration Neuro-humoral activation Reduction in sodium excretion and response to loops diuretics
Diuretics Combination Therapy Thiazides Acetazolamide Aldosterone antagonists Loop Diuretics
Patients admitted with evidence of significant fluid overload should initially be treated with loop diuretics.. When a patient with congestion fails to respond to initial doses of intravenous diuretics, several options may be considered: right heart catheterization a thiazide or spironolactone can be added continuous infusion of the loops diuretic may be considered.. If all diuretic strategies are unsuccessful, ultrafiltration or another renal replacement strategy may be reasonable. Jessup M. et al. Circulation 2009
Small size of studies Performed in the early 1970s Lack of control groups Heterogeneous patient populations Wide variation in diuretic regimens Focus on physiologic rather than clinical outcomes (weight loss, urine volume, sodium excretion) n=373 Jentzer JC et al. JACC 2010
Heart failure and severe fluid overload Congestion Increased CVP Reduction in glomerular filtration Neuro-humoral activation Reduction in sodium excretion and response to loops diuretics
Ultrafiltrazione (SCUF) Venous line Filter Ultrafiltrate Peristaltic pump Arterial line
Separazione per CONVEZIONE Il processo convettivo è caratterizzato dal trasporto contemporaneo di soluti e solvente attraverso una membrana semipermeabile in funzione di un gradiente di pressione transmembrana Acqua e soluti, concentrazione simile alla soluzione originale
Hydrostatic Pressure Ultrafiltrazione - refilling plasmatico - Reduction in extravascular volume No change in intravascular volume Isotonic fluid Plasma refilling Ultrafiltrate Edema Blood Filter Proteins Solutes (<50.000 D)
Clinical Effects of Ultrafiltration in HF Before UF Soon after UF
Marenzi G. et al. JACC 2001
3 months after UF Before UF 3 months after UF Before UF Agostoni PG et al. Am J Cardiol 1995
Marenzi G. et al. JACC 2001
Interrelation of Humoral Factors, Hemodynamics, and Fluid and Salt Metabolism in Congestive Heart Failure: Effects of Extracorporeal Ultrafiltration Marenzi G. et al. Am J Med 1993
Interrelation of Humoral Factors, Hemodynamics, and Fluid and Salt Metabolism in Congestive Heart Failure: Effects of Extracorporeal Ultrafiltration Marenzi G. et al. Am J Med 1993
Changes in circulating norepinephrine with hemofiltration in advanced congestive heart failure. ml/24h Urine output mg/24h Furosemide 3000 400 2500 * * * 320 2000 * 240 1500 1000 160 500 * p<0.001 80 0 Before End 24h 48h 72h UF UF 0 Before End 24h 48h 72h UF UF Cipolla CM. et al. Am J Cardiol 1990
Sustained improvement in functional capacity after removal of body fluid with isolated ultrafiltration in chronic cardiac insufficiency: failure of furosemide to provide the same result UF (n=8; 1710 ml) Furosemide (n=8; 248 mg i.v.) Agostoni PG et al. Am J Med 1994
Loop diuretics can cause clinical natriuretic failure: a prescription for volume expansion Ali SS et al. Congest Heart Fail 2009
Emofiltrazione (CVVH) Replacement fluid Venous line Filter Ultrafiltrate Peristaltic pump Arterial line
Hydrostatic pressure EMOFILTRAZIONE Blood Ultrafiltrate 1L Proteins Solutes < 50.000 D 1L 0.5 L Infusion Fluid
Caratteristiche della Emofiltrazione Unisce i vantaggi di UF e HD (rimuove acqua e contemporaneamente depura il sangue dai soluti) Consente di superare i limiti della HD (ipotensione) Molto più facile da usare della HD (non richiede personale specializzato) Maneggevole: permette di cambiare in corso di trattamento la modalità di sostituzione renale E in grado di dissociare la sottrazione di acqua e sodio (potenziale utilità nello SCC con iponatremia) E in grado di correggere l acidosi
Acqua UF CVVH HD Soluti
Vantaggi dell Emofiltrazione Metodica molto ben tollerata emodinamicamente Ci permette di personalizzare per ogni singolo paziente il target terapeutico e di modificarlo continuamente nel corso del trattamento (maggior efficacia e sicurezza) Consente una più facile introduzione della metodica nella pratica quotidiana cardiologica, sia per il personale medico che quello infermieristico.
The best treatment for severe fluid overload in CHF remains unclear
At 48 hours, patients randomized to ultrafiltration had a greater weight loss Costanzo MR, for the UNLOAD invest. JACC 2007
Costanzo MR, for the UNLOAD invest. JACC 2007
Loop diuretics can cause clinical natriuretic failure: a prescription for volume expansion Ali SS et al. Congest Heart Fail 2009
McMurray JJV. et al. Eur Heart J 2012
McMurray JJV. et al. Eur Heart J 2012
Changes in serum creatinine and weight at 96 hours In 188 CHF patients with WRF (within 12 weeks before or 10 days after index admission for heart failure) The primary end point was the change in creatinine levels and in weight in the first 96 hours. Bart BA et al. (CARESS-HF investigators). NEJM 2012
When UF/CVVH should be used in CHF? Ultrafiltration as a frontline treatment option for all CHF (UNLOAD)? Ultrafiltration as a rescue treatment option for patients with WRF and persistent congestion (CARESS-HF)? Notably, in both trials diuretics were withdrawn or not allowed in ultrafiltration-treated patients!
Continuous Ultrafiltration for congestive heart failure The CUORE trial Multicenter, prospective, randomized, unblinded study enrolling patients with severe CHF Inclusion criteria were: age >18 years, New York Heart Association (NYHA) class III and IV, LVEF <40%, estimated weight gain due to peripheral fluid overload of at least 4 kilograms (8±4 kg) no severe renal insufficiency (creatinine <3 mg/dl) Diuretics were not withdrawn in ultrafiltration group Marenzi G et al. Journal of Cardiac Failure 2013
Continuous Ultrafiltration for congestive heart failure The CUORE trial Screened (n=64) Randomized (n=56) <24 hours Allocated to control group (n=29) Allocated to Ultrafiltration group (n=27) 1-year follow-up 1-year follow-up Primary end point: incidence of re-hospitalizations for CHF in the two groups Marenzi G et al. Journal of Cardiac Failure 2013
Continuous Ultrafiltration for congestive heart failure The CUORE trial Rehospitalizations for CHF Ultrafiltration P=0.0003 Standard therapy Marenzi G et al. Journal of Cardiac Failure 2013
Continuous Ultrafiltration for congestive heart failure The CUORE trial 15 12 9 Body weight reduction at hospital discharge Kg Fluid withdrawal was recommended not to exceed 75% of the estimated initial weight increase, in order to reduce the risk of hypovolemia-induced AKI associated with excessive dehydration. P=0.75 15 12 9 Time required for clinical stabilization days P=0.23 6 6 3 7.5±5.6 7.9±9.0 3 7.4±4.6 9.1±1.9 0 Ultrafiltration Standard therapy 0 Ultrafiltration Standard therapy Marenzi G et al. Journal of Cardiac Failure 2014
Conclusioni Le linee guida cardiologiche e i trial non ci offrono ancora chiare evidenze e raccomandazioni su quando e come utilizzare al meglio l ultrafiltrazione nello scompenso cardiaco congestizio. Questa dovrebbe essere impiegata in pazienti che, pur non ancora ufficialmente refrattari, non hanno le condizioni ideali per poter rispondere al meglio alla terapia diuretica. Il paziente con evidente sovraccarico idrico periferico, ridotta diuresi e natriuresi rappresenta il candidato ideale in cui l ultrafiltrazione è in grado, correggendo l emodinamica renale, di ripristinare una corretta risposta alla terapia diuretica.
Ultrafiltration/CVVH and diuretics should work together