Presentation on theme: "Albumin Infusions: A review of literature pertinent to IM Hospitalists"— Presentation transcript:
1 Albumin Infusions: A review of literature pertinent to IM Hospitalists L Noronha, MDAssistant Professor of MedicineMay 6, 2011
2 Thanks to: Shauna Rodriguez Autumn Roberts Melissa Cordero Richard D’AngioJim LittleChris McFarlandLenka and Chris
3 Is this the face that launched 1,000,000 albumin infusions? UNM DoIM Grand Rounds 4/21/11:Emerging Medical Surgical Strategies in the Management of Advanced CHFMarvin Slepian, MDProfessor of Medicine (Cardiology and Biomedical Engineering), University of ArizonaDirector, Interventional CardiologyDirector, University of Arizona Tissue Engineering LabChairman and Chief Scientific Officer, SynCardia Systems, Inc.
4 Objectives Describe current albumin use at UNM Familiarize hospitalists with major trials evaluating inpatient albumin infusionsSubmit guidelines for inpatient albumin administration by IM hospitalists
5 OutlineWhat is albumin?Purported effectsKey trials forResuscitation (SAFE, SOAP, Cochrane Review)Considerations in cirrhosisRecommendations for Section useThere have been no studies to evaluate the role of albumin in CHF
6 Albumin Any non-glycosylated water soluble protein Moderately soluble in salt solutionsExamples: AFP, Vit D binding protein, HSAAlbuminoids contain albumin (egg white)
7 Human Serum Albumin Negatively charged globular serum protein 585 amino acids3 identical paired subdomains A,BTyrosine, methionine, lysine residuesDisulfide bondsTertiary structureBinding sites!1 free cysteine residueReduced sulphydryl (-SH) moietyInactivates reactive oxygen species
8 More on HSA… Synthesized in liver 30-40% in serum Remainder stored in muscle and skinProduction triggered by decreased oncotic pressure
9 Albumin for the Vascular Space 60% of colloidal oncotic pressureAttracts sodium and other osmotically active positive ions
10 Binding and Transport of Various Compounds EndogenousExogenousUnconjugated bilirubinFree fatty acidsCalciumHormonesNitric oxideMetalsTryptophanLow albumin assoc c HEBinding to albumin “keeps” drug in vascular spaceUnbound drug (free) is activeHigh affinity drugs need to be given in higher dosesLoop diuretics, warfarin, NSAIDS, phenytoin have high affinity
11 Desired Roles of Albumin Infusion Oncotic pressureAnti-inflammatoryDiuretic
12 Albumin for Infusion Pooled from human donors Pasteurized at 60⁰C for 10 hrs.10% leaves intravasc space within 2 hours75% after 2 days (nl capillaries)5% (nl serum osm) for volume expansion25% sol’n for LVP, SBP, HRSOrder sol’n as 0.5mg/kg or #g in Powerchart$36/12.5g at UNMUNM Allocation 600U/month
15 Cochrane Injuries Group Albumin Reviewers - 1998 Meta analysis of 24 studies (combined 1419 pts) evaluating albumin infusion in critical illnessAbsolute increase of death 6% (NNH 17) over NSEditorial: “Albumin use should be halted”Authors recc: “albumin should not be administered to critically ill outside the context of rigorously conducted, randomized trials.”
16 Sepsis Occurrence in Acutely ill Patients (SOAP) – Critical Care 2005 Multi-center prospective observational studyICUs in several European countries3047 pts adm May 1-15, 2002354 received albumin (11.2%), 2793 did not (88.8%)Noted that albumin given to sicker pts (cancer, cirrhosis), so matched crystalloid subgroup compared
17 SOAP ResultsAlbumin associated with decreased ICU and hospital survival (relative hazard 1.57)
18 Saline versus Albumin Fluid Evaluation (SAFE) - NEJM 2004 Multi-center double-blind RCTICUs in NZ, Australia 11/01-6/036997 ICU pts > 18y req fluid resusExcluded: cardiac surgery, liver xplant, burnsRandomized to 4% albumin or NSidentical 500 mL bottles, “masking cartons, IV sets”Add’l fluids, monitoring at provider discretionPrim endpt: 28d mortalitySecondary: LOS (ICU, total), vent days, RRT
19 So SAFE said, “It’s Safe.” SAFE ResultsPrimary and secondary 28 day endpoints equal for albumin and saline groups Subgroup analyses: - Pt baseline albumin did not impact outcomes - Trauma (brain injury) did worseSo SAFE said, “It’s Safe.”
20 Nephrotic SyndromeNefrologia 2011;31(2): | Doi /Nefrologia.pre2010.Nov.10724Avances en la fisiopatología del edema en el síndrome nefróticoNew insights into the pathophysiology of oedema in nephrotic syndromeEnviado a Revisar: 8 Nov. 2010 | Aceptado el: 16 Nov | En Publicación: 22 Mar. 2011H. Rondon-BerriosDivision of Nephrology. Department of Internal Medicine. University of New Mexico School of Medicine. Albuquerque, Nuevo México (EEUU)Correspondencia para H. Rondon-Berrios, Division of Nephrology. Department of Internal Medicine, University of New Mexico School of Medicine, ACC 5. MSC University of New Mexico, , Albuquerque, Nuevo México, EEUUForget albumin. It’s all about the Epithelial Sodium Channel!
22 Diuresis in CirrhosisEffects of Albumin/Furosemide Mixtures on Responses to Furosemide in Hypoalbuminemic Patients, Chalasani, et al, J Am Soc Nephrol, 200113 Patients with cirrhosis already on spironolactone and dietary sodium restriction ALL receive different doses of furosemide with or without albumin.No difference in diuresis (volume, urine sodium) or furosemide activity
23 Albumin for Diuresis in Cirrhosis Mixed results in randomized studiesHeterogeneous baseline patientsDefinitions of “refractory ascites”Renal functionMay decrease hospital LOSDoes not impact survivalMay be cost effective
24 Large Volume Paracentesis LVP preferable to serial 5L paracentesis + diuretics for refractory ascites in 5 RCTs - Decreased LOS - Fewer re-admissions * Refractory ascites = persists despite doses of spironolactone furosemide 160 daily or recurs rapidly after LVP Mean survival = 6mos.
25 Albumin (20% sol’n) Decreases Paracentesis Induced Circulatory Dysfunction (PICD) in RCT’s With or without albumin – 105 ptsAlbumin (18.5%) vs other volume expanders [Dextran 70 (34.4%), Polygeline(37.8%)] – 289 pts*PICD = increase in plasma renin activity on the sixth day after paracentesis of more than 50% of the pretreatment value- correlated with time to readmission and survivalRange of 5-10g albumin/L paracentesis used
26 SBP Multicenter RCT in Spain EFFECT OF INTRAVENOUS ALBUMIN ON RENAL IMPAIRMENT AND MORTALITYIN PATIENTS WITH CIRRHOSIS AND SPONTANEOUS BACTERIAL PERITONITIS, Sort, et al, NEJM, 1999Multicenter RCT in Spaincefotaxime (63 pts) or cefotaxime + IV albumin 20% sol’n (63)IV albumin grp received 1.5 g/kg on diagnosis (day 1), 1 g/kg on day 3.Primary endpt: non-reversible deterioration in renal function (Cr incr to > 1.5 or Cr incr > 50% over baseline) during hospitalizationFollowed for 90 days
27 ResultsIncidence of renal impairment was lower among those treated with cefotaxime + albumin (6 of 63 [10%]) compared to cefotaxime alone (21 of 63 [33%]), P= [NNT= 4 ; (33-10=23), 1/.23= 4]In-hospital mortality was lower among those treated with cefotaxime + albumin vs. those treated with cefotaxime alone (10% vs 29%, P=0.01). [NNT= 5 (29-10=19), 1/.19= 5]Mortality at 3 months was also lower among those treated with cefotaxime + albumin vs. those treated with cefotaxime alone (22% vs 41%, P=0.03). [NNT= 5 (41-22= 19), 1/.19= 5]For the entire series of patients, independent predictors for developing renal impairment were: baseline serum bilirubin and Cr levels (P<0.001 and 0.01, respectively).
28 HRSTerlipressin therapy with and without albumin for patients with hepatorenal syndrome: Results of a prospective, nonrandomized study, Ortega, Hepatology 2002Single center. Sept 1999-May 200121 patients. HRS per IAC CriteriaAll given 60-80g IV albumin over 2 days8 have LVP with more albuminAll start terlipressinFirst 13 receive more albumin 20% sol’n: 1g/kg Day 1, then 20-40g/dFinal 8 do not receive add’l albumin.More “responders” in albumin group, alive in 1 month, transplanted.No randomization!
29 Albumin for HRS No randomization! Treatment of Hepatorenal Syndrome as Defined by the International Ascites Club by Albumin and Furosemide Infusion According to the Central Venous Pressure: A Prospective Pilot Study, Peron, Gastroenterology 200520 patients with HRSAlbumin to keep CVP > 3 (no limit) + Furosemide (to maintain UO > 50mL/h) given 250mg over 4h, increased for up to 1.5g/dRange 40 to 600g albumin/day11 patients “responded” (Cr clearance rose to > 40).No randomization!
30 This created pressure… As seen in “Deathly Hallows: Part 2” Use albumin in HRS!NephrologistHospitalist
31 HRSTerlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Martin, Gastroenterology 200846pts with HRS randomized to:terlipressin + albumin or albumin aloneImproved renal function without survival benefitSeveral subsequent studies built on adding vasoactive medications to albumin.
32 Section Recommendations LVP (> 5L) 25% albumin: 5-10g/L removed (as bolus) SBP 25% albumin: 1.5g/kg on dx, 1g/kg on Day 3
34 100g, 75g50gConsider giving 75g for 10L or more paracentesis
35 Section Recommendations HRS 20 or 25% albumin sol’n in consultation with nephrology Stay tuned for emerging data on vasopressin analogues, prostaglandins,
36 Additional References Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomized controlled trials. BMJ. 1998;317:235–40. Bunn F, Lefebvre C, Li Wan Po A, et al. Human albumin solution for resuscitation and volume expansion in critically ill patients: The albumin reviewers. Cochrane Database Syst Rev :CD Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247–56. Vincent JL, Navickis RJ, Wilkes MM. Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials. Crit Care Med. 2004;32:2029–38. SAFE Study Investigators. Finfer S, Bellomo R, McEvoy S, et al. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study. BMJ. 2006;333:1044–9. Quinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and therapeutic potential. Hepatology. 2005;41:1211–9. Gentilini P, Casini-Raggi V, Di Fiore G, et al. Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial. J Hepatol. 1999;30:639–45. Chalasani N, Gorski JC, Horlander JC, et al. Effects of albumin/furosemide mixtures on responses to furosemide in hypoalbuminemic patients. J Am Soc Nephrol. 2001;12:1010–6. Gines P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet. 2003;362:1819–27. Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999;341:403–9. Akcicek F, Yalniz T, Basci A, et al. Diuretic effect of furosemide in patients with nephrotic syndrome: is it potentiated by intravenous albumin? BMJ. 1995;310:162–3. Peron JM, Bureau C, Gonzalez L, et al. Treatment of hepatorenal syndrome as defined by the international ascites club by albumin and furosemide infusion according to the central venous pressure: a prospective pilot study. Am J Gastroenterol 2005;100(12): Martin-Llahi, M, Pepin, MN, Guevara, M, et al. Terlipressin and albumin versus albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008;134: