1. Fact The evidence base for most of what we do in intensive care is rather poor

4. Albumin - properties Volume expansion 4% x 0.8, 5%, 20% x 3 Maintenance of colloid osmotic pressure (COP) –Need a lot….no effect on other serum proteins.. Binding and transport - drugs (frusemide, antibiotics) toxins….. Free radical scavenging Immunological : stimulatory and inhibitory Anticoagulatory effects and Procoagulatory effects : –inhibit plat aggregation, inhibition of factor Xa by ATIII, TEG shows early hypocoagulable effects Tobias et al, Jorgensen et al Vascular permeability and over albuminisation Qiao et al What are we prescribing 5%, 20%, 25% +/- crystalloid Aluminum toxicity, hypotension (vasoactive peptides) Myocardial depression (animal work ; Ca binding)

10. Wild mice Rage -/- mice Post transcriptional Proteins Advanced glycylation end product

11. HAS and HES increased No rolling and decreased adherence and aggregation Albumin decreased activation of No and platelets Albumin and HES decrease E Selectin release Alb and HES decrease to varying degrees decrease No : endothelial interactions

12. Albumin : Sepsis and thiol repletion Quinlan et al, Clinical Science 1998 95, 459 200 ml 20% albumin or placebo

13. Which fluid ……SOAP-study Role of balanced solutions - acidosis, consider Cl levels

19. 37 ventilated acute lung injury Total protein < 5 g/dl 5 day protocol of 25 g of 25% HAS 8 hrly + frusemide or placebo Frusemide titrated to weight loss > 1kg/day Total protein 1.9 vs 0.7 g/dl Albumin 1.5 vs 0.3 g/dl Increased COP 8.3 vs 2.9 mmHg at study end Weight loss 10 vs 4.7 Kg Increased Na, HCO3 and decreased K No change in creatinine Albumin and frusemide in hypoalbuminaemia in ALI Martin G Crit Care Med 2002 ; 30:2175

20. Improved oxygenation : improved Pa02/Fi02 ratio by 40% No difference in PEEP No changes in SOFA scores, shock free days or rates of re-intubation No difference in % requiring mechanical ventilation

21. Acute kidney injury

22. mortality

28. Albumin and diuretics and ascites 126 cirrhotics ascites Diuretics vs Diuretics + Alb 12.5 g/day Diuretics vs Diuretics + Alb 25g/week as outpatient. Follow up over 3 yrs Hospital stay shorter in Alb grp 20±1 vs 24±2 days p<0.05 Risk of developing ascites lower in Alb grp –19%, 56%, 69% vs 30%, 74%, 79% (p<0.02) Survival similar in both groups Gentilini et al J Hepatol 30(4):639 1999

29. Terlipressin and albumin vs albumin Martin-Llahi M Gastroenterology 2008:134 1-2 mg 4hrly Albumin daily 1g/kg N=23 each grp Improved renal function 43 vs 8% No difference in 2 mnth survival CVS complications –4 Alb vs 10 T + Alb

30. RCT Terlipressin in Type I HRS Sanyal A Gatroenterology 2008 :134:1360 1 mg 6 hrly vs placebo Albumin in both groups If no response (30% decrease in creat) at day 4 : to 2mg 6 hrly 14 days Rx : 56 in each grp Success defined as creatinine < 1.5 mg/dl for 48 hrs by Day 14 Rx success : 25 vs 12.5 % Baseline to day 14 decrease in creatinine 0.7 vs 0 mg/dl Similar survival between grps HRS reversal improved 180 day outcome

31. Terlipressin + Albumin vs Albumin

32. 10 trials only type I and II Drug ± alb vs no intervention Vasoconstrictors + Alb : Effect on mortality at 15 days but not at 30, 90 or 180 days RR 0.6 (0.37-0.97) Terlipressin + Albumin vs Albumin : decreased mortality in type I RR 0.83 (0.65-1.05)

33. Multivariate – baseline creatinine

34. SBP frequently associated with renal failure Associated with decreased effective blood volume and high mortality 126 patients iv cefotaxime or iv cefotaxime plus albumin (1.5g/kg) at day 0 and day 3 (1.0 g/kg) 94% and 98 % had resolution of infection Renal failure in 21 (33%) cef grp vs 6 (10%) in alb/cef grp p=0.002 Mortality 18 (29%) vs 6 (10%) At 3 months the mortality was 41% vs 22% p=0.03 Albumin and renal impairment in patients with cirrhosis and SBP Sort P et al N Engl J Med 1999 5; 341 (6):403

35. HAS (4.5%) vs HES (6%,0.5) in paracetamol hepatotoxicity: prospective cohort study Bernal W Lancet 2001 AlbuminHES Number5151 Age35 (20)35 (22) Apache II14 (17)15 (16) INR3.3 (2)3.3 (2.6) Creatinine124 (132)142 (167) ARF o/a14 (27%)17 (33%)

36. Albumin HES Crystalloid (72 hrs) ml6237 (6086)6670 (6078) ml/kg29 (42)38 (52) Colloid (72 hrs) ml2000 (2875)3000 (2812) ml/kg 96 (104)112 (92) No differences in creatinine at any time point RRT (n)24 (47%)25 (49%) Death / LT 19 (37%)22 (44%) ICU stay3 (6)2 (11) No relationship between colloid used and ARF on multivariate analysis No difference if established ARF patients are excluded from study

38. Today’s evidence.. tomorrow’s chip paper?

39. 20 patients with SBP : randomized within 12 hrs 1.5 g/kg at day 1 and 1.0 g/kg at day 3 20% albumin given over 6 hours 18 hrs HES 6% given over 18 hours Well matched Studied at resolution of SBP ( ascitic taps)

42. terlipressin placebo Hepatology 2011 3 mmHg MAP, Bilirubin

46. plasmapheresis standard Rx 67% 46% NNT 5

47. Recognize Fluids and CVS status Ventilatory issues Drain ascites Ileus : stop feeding Ng drainage, flatus tubes Open abdomen Incidence 8 - 50%

49. Ligand binder, extracellular metal ion-binding and radical- scavenging antioxidant. Baseline bloods 200 ml 20% albumin or placebo Alb 12.6, 22.3, 19 mg/ml at 0, 5min and 4 hrs Thiol levels rose 138, 192, 192 uM at 0, 5min and 4 hrs Thiol levels remain elevated for 8 hrs - (33% of rise lost at 4 hrs) Albumin : Sepsis and thiol repletion Quinlan et al, Clinical Science 1998 95, 459

50. TypeSolvensVol Exp Hypo-oncoticGelofusinNaCl0.8 Albumin 4%NaCl0.8 Iso-oncoticAlbumin 5%NaCl1 Hyper-oncoticHEA 6%-10% 200/0.5NaCl1.2 Voluven 6% 130/0.4NaCl1.2 Albumin 20%3-4 Hyper-oncotic, hypertonic HEA 6% 200/0.5HS 7.2%3 Dextran 70 6%HS 7.5%3

51. Terlipressin ± albumin Ortega et al Hepatology 2002;36:941 0.5 mg 4 hrly, albumin 1g/kg/body weight day 1 then 20 - 40 g/day

55. 68 patients : fluids for paracentesis, renal dysfunction or hyponatraemia

56. Sanyal A Gatroenterology 2008 :134:1360