FactThe evidence base for most of what we do in

intensive care is rather poor

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)

Wild mice

Rage -/-mice

Post transcriptional ProteinsAdvanced glycylation end product

HAS and HES increased No rolling and decreased adherence and aggregationAlbumin decreased activation of No and platelets Albumin and HES decrease E Selectin release

Alb and HES decrease to varying degrees decrease No : endothelial interactions

Albumin : Sepsis and thiol repletionQuinlan et al, Clinical Science 1998 95, 459

200 ml 20% albumin or placebo

Which fluid ……SOAP-study

Role of balanced solutions - acidosis, consider Cl levels

• 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

Improved oxygenation : improved Pa02/Fi02 ratio by 40%

No difference in PEEP

No changes in SOFA scores, shock free days or rates ofre-intubation

No difference in % requiringmechanical ventilation

Acute kidney injury

mortality

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

Terlipressin and albumin vs albuminMartin-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

RCT Terlipressin in Type I HRSSanyal 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

Terlipressin + Albumin vs Albumin

10 trials only type I and IIDrug ± 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 IRR 0.83 (0.65-1.05)

Multivariate – baseline creatinine

• 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

HAS (4.5%) vs HES (6%,0.5) in paracetamol hepatotoxicity: prospective cohort study

Bernal W Lancet 2001

Albumin HES Number 51 51 Age 35 (20) 35 (22) Apache II 14 (17) 15 (16) INR 3.3 (2) 3.3 (2.6) Creatinine 124 (132) 142 (167) ARF o/a 14 (27%) 17 (33%)

Albumin HES Crystalloid (72 hrs) ml 6237 (6086) 6670 (6078) ml/kg 29 (42) 38 (52) Colloid (72 hrs) ml 2000 (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 stay 3 (6) 2 (11) No relationship between colloid used and ARF on multivariate analysis No difference if established ARF patients are excluded from study

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

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)

terlipressin

placebo

Hepatology 2011

3 mmHg MAP, Bilirubin

plasmapheresis standard Rx

67%

46%

NNT 5

Recognize

Fluids and CVS status

Ventilatory issues

Drain ascites

Ileus : stop feeding

Ng drainage , flatus tubes

Open abdomen

Incidence 8 - 50%

• 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 repletionQuinlan et al, Clinical Science 1998 95, 459

Type Solvens Vol Exp

Hypo-oncotic Gelofusin NaCl 0.8

Albumin 4% NaCl 0.8

Iso-oncotic Albumin 5% NaCl 1

Hyper-oncotic HEA 6%-10% 200/0.5 NaCl 1.2

Voluven 6% 130/0.4 NaCl 1.2

Albumin 20% 3-4

Hyper-oncotic, hypertonic

HEA 6% 200/0.5 HS 7.2% 3

Dextran 70 6% HS 7.5% 3

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

68 patients : fluids for paracentesis, renal

dysfunction or hyponatraemia

Sanyal A Gatroenterology 2008 :134:1360